* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Membrane Remodeling and Organization: Elements Common to
Biochemical switches in the cell cycle wikipedia , lookup
Lipid bilayer wikipedia , lookup
Magnesium transporter wikipedia , lookup
Cell culture wikipedia , lookup
Cellular differentiation wikipedia , lookup
Cytoplasmic streaming wikipedia , lookup
Cell encapsulation wikipedia , lookup
SNARE (protein) wikipedia , lookup
Protein phosphorylation wikipedia , lookup
Cell growth wikipedia , lookup
Extracellular matrix wikipedia , lookup
Cell nucleus wikipedia , lookup
Lipopolysaccharide wikipedia , lookup
Organ-on-a-chip wikipedia , lookup
Type three secretion system wikipedia , lookup
Signal transduction wikipedia , lookup
Trimeric autotransporter adhesin wikipedia , lookup
Cytokinesis wikipedia , lookup
Cell membrane wikipedia , lookup
Critical Review Membrane Remodeling and Organization: Elements Common to Prokaryotes and Eukaryotes Luz A. Vega-Cabrera pez Liliana Pardo-Lo noma de Me xico, Instituto de Biotecnologıa, Universidad Nacional Auto xico Apdo. Postal 510-3, Cuernavaca, Morelos, Me Abstract Membrane remodeling processes in eukaryotes, such as those involved in endocytosis and intracellular trafficking, are mediated by a large number of structural, accessory and regulatory proteins. These processes occur in all cell types, enabling the exchange of signals and/or nutrients with the external medium and with neighboring cells; likewise, they are required for the intracellular trafficking of various cargo molecules between organelles, as well as the recycling of these structures. Recent studies have demonstrated that some elements of the molecular machinery involved in regulating and mediating endocytosis in eukaryotic cells are also present in some bacteria, where they participate in processes such as cell division, sporulation and signal transduction. However, the mechanism whereby this prokaryotic machinery carries out such functions has barely begun to be elucidated. This review summarizes recent information about the cytoskeletal and membrane-organizing proteins for which bacterial homologs have been identified; given their known functions, they may be considered to be part of an ancestral membrane organization system that first emerged in prokaryotes and which further evolved into the more complex C 2017 IUBMB Life, regulatory networks operating in eukaryotes. V 69(2):55–62, 2017 Keywords: Bacillus subtilis; membrane elements; cytoskeleton; actin; tubulin; flotillin; dynamin; arrestin Introduction For decades, the main characteristic used to distinguish prokaryotic from eukaryotic cells has been the presence of membrane-bounded organelles in the later, including an endomembrane system that enables the exchange and traffic of substrates among these structures. The eukaryotic endomembrane system is a dynamic network of membranes, whose evolutionary origin can be traced to the eubacteria ancestral group (1). These organisms lack a cell wall, and their cell membranes are composed of lipid esters; these lipids are C 2017 International Union of Biochemistry and Molecular Biology V Volume 69, Number 2, February 2017, Pages 55–62 pez, Instituto de Biotecnologıa, *Address correspondence to: Liliana Pardo-Lo noma de Me xico, Apdo. Postal 510-3, Cuernavaca, Universidad Nacional Auto xico. Tel: 152-777-3291-624. Fax: 152-777-3291-624. Morelos 62250, Me E-mail: [email protected] Received 14 November 2016; Accepted 15 December 2016 DOI 10.1002/iub.1604 Published online 23 January 2017 in Wiley Online Library (wileyonlinelibrary.com) IUBMB Life capable of bearing a load of folding and invaginations, which are believed to have gradually specialized, eventually giving rise to the organelles now recognized in eukaryotes (2). De Duve and Wattiaux (1966) have proposed that the evolutionary force behind the emergence and permanence of this endomembrane system was the energetic and metabolic advantage offered by the intracellular digestion of substrates. Having this tool, heterotrophic organisms do not have to restrict their residence to sites of high nutrient availability. Another advantage of this system is the elimination of toxic agents that cells can perform when they internalize bacteria and other cargoes, and degrade them in specialized organelles, such as lysosomes (3). With the advent of this new system, all the intracellular architecture was modified. Cytoskeletal proteins—such as actin, tubulin and clathrin—were originally thought to have emerged in events subsequent to the prokaryote–eukaryote evolutionary separation. Recently, however, protein homologs of various eukaryotic cytoskeletal elements have been found in prokaryotes; these homologs have been associated to bacterial processes related to membrane remodeling and cytoskeleton organization (4,5). De Duve (3) has proposed that this finding 55 IUBMB LIFE could be indicative of these elements having emerged at par with the acquisition of the internal system of membranes, enabling the mobility of the elements that shape the network as well as their proper functionality. Additionally, it could be considered as an indicator of the evolutionary conservation of proteins involved in the organization of the plasma membrane and of its dynamics during processes such as cell division; these transcendental functions require a complex regulation that up until recently was thought to be absent in ancestral organisms. In this review, we summarize information about plasma membrane organization systems and the cytoskeleton, whose bacterial counterparts have been described and associated to processes of membrane remodeling, such as cell division and sporulation. The existence of such functional associations prompt us to suggest that these fundamental processes might represent an ancestral system that initially appeared in prokaryotes and was maintained in eukaryotes, where it has evolved into a complex intracellular network for the transport of nutrients and waste materials. PVC Superphylum: A Special Case of Shared Characteristics When the division of the three domains of life arose it was established that two kinds of cells conformed them; prokaryotic cells integrating the Bacteria and Archaea domains and eukaryotic cells representing the domain Eukarya. The differences that were determined as distinctive of these two cells were the existence in the later of a nucleus surrounded by an envelope that separates the genetic material from the rest of the cell and an endomembranous system, composed of organelles with specialized functions and an internal membrane network that connects these organelles and allowed traffic of substrates from and towards the plasma membrane. This distinction was first challenged with the discovery of a prokaryote phylum that shared some of these eukaryotic distinctive features, the Planctomycetes (6). To date, the particular characteristics of Planctomycetes have been demonstrated to exist in other bacterial phyla (7), allowing the emergence of the PVC (from Planctomycetes, Verrucomicrobiae and Chlamydiae) superphylum, that includes the Planctomycetes, Verrucomicrobiae, Chlamydiae, Poribacteria, Lentisphaerae and the OP3 candidate phyla (8). These organisms share a set of special features that differentiate them from the whole set of known bacteria and make them more similar to archaea or eukaryotes (reviewed in (8,9)): its internal membrane is invaginated, conforming the intracytoplasmic membrane (ICM) that separates the cell in different compartments, the paryphoplasm and the riboplasm, which contains the ribosomes and nucleoid. Members of the genus Gemmata sp. have nuclear organization and condensation similar to histones (10). Referent to the membrane organization, they are the only bacteria that contain homologs of 56 membrane coat proteins (11) and structures that could be catalogued as specialized organelles, as is the case of the ammonium metabolism organelle, anammoxosome (12). The lipids present in their membranes are typical of eukaryotes and they can synthesize sterols (13), important regulators of membrane fluidity that can be involved in the ICM invaginations (8). The PVC members divide by budding independent of FtsZ, an important cell division protein among bacteria, and its cell wall lack peptidoglycan; instead it is composed mainly of proteins (14). However, FtsZ homologs, tubulin homologs or both, can be found in their genomes (15). Finally, members of the genus Gemmata sp. are able to internalize totally folded proteins in an energy-dependent and receptor-mediated process (16), similar to endocytosis, previously thought to be specific of eukaryotic cells. The discovery of the PVC superphylum has open a controversial discussion about the cell complexity emergence, and even has allowed the occurrence of a new proposal, the cauldron hypothesis, which suggest continuity between the three domains of life (9). However, PVC features are singular; they are not distributed among all bacteria. Instead, most bacterial membranes contain only some homolog elements that are shared with eukaryotes and give them common organizational and functional similarities. Organization of the Plasma Membrane Biological membranes are composed of lipids and proteins organized into microdomains —structures that generate a heterogeneous distribution of these components-, which is essential for their functionality. In the case of eukaryotic membranes, specialized proteins may be arranged into structures called membrane rafts or lipid rafts, which are enriched in special lipids, such as cholesterol, and are important for the functionality of several cellular processes (reviewed in ref. 17). The organization of these lipid rafts has been considered to be a distinctive element in the evolution of cellular complexity, and as such, an exclusively eukaryotic element. However, functional membrane microdomains (FMMs) have been recently discovered in bacteria, along with bacterial lipid rafts where specific proteins are arranged, such as those involved in signal transduction and secretory processes (18). The presence of these structures in bacteria points to the existence of complex prokaryotic membrane organization systems. While eukaryotic lipid rafts are characterized by the presence of cholesterol and sphingolipids (17), the formation of these structures in bacteria depends on the aggregation of poly-isoprenoid lipids with a structure similar to that of cholesterol and whose presence is related to membrane fluidity (19) (further information is reviewed in refs. 18,20). In addition, bacterial membranes contain noncyclic poly-isoprenoid lipids, such as carotenoids, which regulate membrane rigidity (21) and are important constituents of FMMs (22). Cardiolipin is a diphosphatidylglycerol-like lipid found in the internal membrane of mitochondria. In bacteria, Conserved Elements in Membrane Organization cardiolipin is necessary for the control of membrane fluidity under stress conditions, and it is found in membrane domains, mainly in the cell poles and the septum region, both in Escherichia coli and Bacillus subtilis (23,24). It has been proposed that cardiolipin is a constituent element of FMMs, and that it partakes in the recruitment of proteins that require to be localized in these structures for their proper functionality (18,22,24). The localization pattern of this lipid was found to be related to cell division and differentiation processes (24). In addition to their differential lipid composition, membrane rafts are enriched with specific proteins, such as flotillins, whose role is to recruit additional proteins to the rafts to facilitate their interactions and oligomerization (25,26). In eukaryotes, flotillins are involved in plasma membrane organization, cytoskeletal rearrangements, signal transduction, endocytosis and chromosome segregation during mitosis (information reviewed in refs. 27,28). Flotillins are elements conserved among vertebrates and invertebrates, and they are ubiquitous. They belong to a family of proteins that contain a conserved SPFH (Stomatin, Prohibitin, Flotillin, HlfK/C) N-terminal domain and a C-terminal domain required for their oligomerization (29). Flotillin homologs have been identified in B. subtilis (Fig. 1A), namely FloA and FloT; they are localized in FMMs (30) and have been related to the recruitment of integral membrane proteins (31), the localization and functionality of certain transport proteins (31,32) and the formation of structures that promote membrane fusion and invagination during cell division and sporulation (30,33). It has been demonstrated that B. subtilis flotillins can be clustered into domains in eukaryotic cells, even in the absence of any other bacterial elements (32), suggesting their function is evolutionarily conserved. Similarities and special characteristic of eukaryotic and prokaryotic flotillins are summarized in Table 1. The absence of flotillins in B. subtilis leads to alterations of diverse processes; for example, it causes decreased sporulation and genetic competence, it alters membrane integrity and cell motility (32), and septum formation does not occur in an efficient fashion (30). In general, the involvement of flotillins in all these cellular processes is related to their ability to organize the plasma membrane and to recruit the specific proteins involved in these processes into membrane domains. It is conceivable that all bacteria might contain FMMs, since at least one copy of a flotillin gene has been identified in all fully sequenced bacterial genomes. While the mechanism of action of bacterial flotillins has been characterized in Gram-positive bacteria, it remains to be fully elucidated in Gram-negative bacteria (48). The presence of FMMs in bacteria, along with their specific lipid and protein composition, indicate their evolutionary conservation, presumably due to the functional importance that their existence implies. Additional to flotillins, small GTPases constitute essential signaling membrane elements that are conserved between eukaryotes and prokaryotes. Similarities and particular characteristics are mentioned in Table 1. In eukaryotic cells, Ras Vega-Cabrera and Pardo-Lopez superfamily of small GTPases are ubiquitous proteins, divided in five families according to their sequences and functionality: Ras, Rab, Rho, Arf and Ran, that regulate vesicular transport, signaling, nucleocytoplasmic transport, actin dynamics, cell motility and polarity (34). In prokaryotes the MglA and Rup families of small GTPases have been identified through a phylogenomic analysis (35); they are involved in development (49), antibiotic resistance (50) and regulation of cell polarity (51); however, the majority of the members of these families have not been experimentally characterized. Both, eukaryotic and prokaryotic small GTPases act as molecular switches that contain a single G domain that cycles between the GDP-bound, or inactive form and the GTP-bound, or active form. They share structural common motifs and its active form interacts with downstream effectors to trigger the specific cell responses (34,35). Previously, the existence of small GTPases was considered to be exclusive to eukaryotes, nevertheless, the discovery of homologs in prokaryotes suggests that they might have an evolutionary origin, reflected in the conserved structure and functionality, and an ancestry relationship has been suggested (52). This would have important evolutionary implications, since these proteins are involved in the eukaryotic compartmentalization and transport, then their emergence would be related to the arose of these eukaryotic features (52). Cytoskeleton Elements Cytoskeleton elements in eukaryotic cells are essential for the regulation of cell shape, motility, cell division, intracellular trafficking and phagocytosis, among other cellular processes. During several years these elements were believed to have eukaryotic origins; however, the existence of bacterial protein complexes that resemble the organization of the eukaryotic cytoskeleton has been recently demonstrated. The most important examples are MreB, the protein homolog of actin, and FtsZ, the homolog of tubulin, which are involved in maintenance of cell shape and cell division, respectively. Table 1 resumes similarities and special characteristic of both, eukaryotic and prokaryotic actin and tubulin. Actin is one of the most abundant proteins in eukaryotic cells; it consists of globular monomers that assemble into actin filaments through an ATP-dependent process. The organization of these filaments within the cell is the main determinant of the cell’s shape. Actin polymerization is a very dynamic process that has been widely studied in eukaryotes (37,53); it is involved in several cellular functions, including intracellular trafficking, endocytosis and morphology maintenance. Actin homologs among eukaryotes share high similarity both in their structure and in their ability to polymerize into filaments (4,54). A group of proteins with a relatively low sequence similarity to actin has been described in bacteria; it is called the MreB protein family, or bacterial actins. These proteins share conserved amino acid motifs clustered around an ATP binding site, which is an essential feature in the structure of all actins 57 IUBMB LIFE FIG 1 Ribbon structure comparisons of eukaryotic cytoskeleton elements and proteins related to membrane organization with their prokaryotic homologs. Sequence similarity values between the eukaryotic protein and its prokaryotic counterpart are low; however, their tridimensional structure is very similar and it is related to an evolutionarily conserved function. (A): SPFH domain of the flotillin family of proteins (PDB number D1WINA). For the FloT protein, we obtained a threading model using the Phyre2 commercial software (47). (B): Monomeric actin (PDB numbers 2HF3 and 1JCF). (C) a-b tubulin (PDB numbers 1JFF and 1FSZ). (D): Dynamin (PDB numbers 3W6N and C2J69D). (E): N domain of the arrestin family of proteins (PDB numbers 4GEJ and 5CL2). (4,54,55). Bacterial actins also contain additional domains according to their unique specialized functions (56); for example, the Hsp70 chaperone contains a peptide-binding pocket required for it to proofread the structure of proteins (56). FtsA is another member of this family; its structure is more similar to that of eukaryotic actin and it has additional domains that 58 allow it to bind to the cell membrane (57), to interact with FtsZ (58) and to participate in cell division (36). Finally, this protein family also includes two cell shape determinants, namely MreB and Mbl (55). MreB and Mbl are the bacterial proteins that exhibit the highest degree of similarity with eukaryotic actin, both Conserved Elements in Membrane Organization TABLE 1 Similarities and special characteristic of the eukaryotic and prokaryotic membrane organization homologs Protein or protein family Similarities Eukaryotic special characteristics Prokaryotic special characteristics Flotillin Conformation of lipid rafts allowing functional membrane domain organization and signaling; SPFH domain (22,31) Involvement in endocytosis and vesicle sorting and trafficking; participation in signal transduction pathways through receptor tyrosine kinases (27) Participation in sporulationrelated processes, biofilm formation, competence and cell division (30,32) Small GTPases Contain a single G domain, capacity to bind GDP/GTP to activate signal transduction pathways; GTP hydrolysis; participation in the regulation of cell polarity (34,35) Participation in nucleocytoplasmic transport and vesicle transport; members of the eukaryotic Ras superfamily are post-translationally modified by lipids, to allow membrane binding (34) Involvement in antibiotic resistance, participation in signal transduction in two component systems (35) Actin/MreB Capacity to polymerize and act as cell shape determinants; interaction with cell membrane and other cytoskeleton elements; ATP binding (36) Polar organization of the actin filaments, which allows spatial organization of the cell; association with motor proteins; participation in cytokinesis, phagocytosis and motility (37) Bacterial actins contain additional domains that specify their functions, such as chaperones or cell division elements; association with PBPs to direct cell shape determination and elongation (38–40) Tubulin/FtsZ Involved in cell division; capacity to polymerize; interaction with other cell division and cytoskeleton proteins; GTPase activity (36) Association with motor proteins; conformation of the mitotic spindle during chromosome segregation; conformation of flagella and cilia; positioning of the cellular organelles (41) Conformation of the Z ring during cell division and sporulation; recruitment of other elements of the divisome; association with PBPs to define cellular location of the cell wall (39,40) Dynamin/DynA GTPase activity; capacity to oligomerize; participation in membrane fusion and membrane remodeling processes (42,43) Helicase activity during scission of membranes in endocytosis; participation in cytokinesis and organelles division (42) Capacity to fuse membranes in vitro in a process independent of GTP, dependent of Mg12 (43); it is located to the division site and it has been related to cell division possibly through interaction with flotillins (33) Arrestin/Spo0M Tertiary structure conservation of the N domain, involved in receptor specificity (44,45) Ability to interact with a wide variety of receptors and act as molecular adaptors in signaling; presence of a C domain that allows oligomerization and endocytosis-related proteins interaction (44) Regulation of sporulation (45); C terminal domain of Spo0M has structural homology with a human proteasome inhibitor protein, the functional implication of this finding is unknown (46) structurally and functionally (59) (Fig. 1B), and just as their eukaryotic homolog, they are involved in cell shape maintenance (55,60). B. subtilis mreB null mutants are not viable, while an inducible mreB null mutant exhibits diminished growth rate, an altered morphology (cells have a rounded shape), and is susceptible to lysis (55). Mbl is not essential for B. subtilis; mbl null mutants exhibit cell shape defects, for Vega-Cabrera and Pardo-Lopez example, bacilli are bent at irregular angles, are wider than the wild type and have membrane protuberances (60). Homologs of MreB and Mbl exist in diverse bacterial and archaeal genera; however, these proteins are not present in coccoid bacteria. Apparently, cells acquire a spherical shape by default, while more complex shape phenotypes require an MreB-like system to properly organize cell morphology (61). 59 IUBMB LIFE It has been suggested that the distinct architecture of MreB and Mbl filaments is related to their unique functions in different aspects of cell morphology. On one hand, MreB appears to control cell width, forming short structures that localize in the middle of the cell, almost perpendicular to its longitudinal axis, thus regulating the cell’s diameter. On the other hand, Mbl maintains orientation and shape in the longitudinal axis of the cell, forming longer structures that extend from one cell pole to the other (55,60). Rather than acting as a scaffold, MreB and Mbl probably work in conjunction with the cell wall synthesis machinery. The cell wall is a complex bacterial structure that maintains cell shape and its main constituent is peptidoglycan. Peptidoglycan is a macromolecular complex synthesized by Penicillin Binding Proteins (PBPs) that function as glycosyl-transferases and transpeptidases, synthesizing and linking glycan and peptide chains (62). It has been proposed that MreB filaments direct peptidoglycan synthesis, and that together, these structures regulate cell shape (54,55). Another function that could be attributed to MreB is the organization of high-fluidity membrane domains (54) that promote the activity of certain proteins by reducing membrane viscosity and by stimulating their catalytic activity and/or their diffusion (54). In eukaryotes, actin participates in the maintenance of lipid rafts (63,64) and by doing so, in the localization and diffusion of integral membrane proteins (65). It is thus conceivable that the ability that MreB and actin have to induce and organize membrane domains could have a common evolutionary origin. Further details on the functional diversity of bacterial homologs of actin have been reviewed elsewhere (38,39,61). Thereby, bacterial cells contain structures with at least one function that is conserved in the eukaryotic actin cytoskeleton: cell shape maintenance. Jones et al. (2001), have proposed that the MreB protein family and actin evolved from a common ancestor that would have emerged before the eukaryote–prokaryote divergence (55). Besides actin, another important component of the eukaryotic cytoskeleton consists of microtubules. Microtubules constitute a transporting system formed by motor intracellular proteins that facilitate vesicle trafficking and dynamics in the eukaryotic endomembrane system. Microtubules are primarily composed of tubulin. In bacteria, FtsZ is a homolog of tubulin that participates in the process of cell division, where it is the main constituent of the Z ring, a structure formed in the future site of division, and which is constrained to mediate cytokinesis (5). Just as in the case of actin, the degree of sequence identity between tubulin and FtsZ is not high, but yet they have a very similar protein structure and they both possess GTPase activity (Fig. 1C), supporting that these two proteins have a common ancestor (66). The process of cell division in bacteria is not simple; it requires the participation of an entire group of positive and negative regulators for the assembly of the Z ring. The entire molecular machinery receives the name of divisome. The positive regulatory elements stabilize the ring in the membrane 60 and avoid its depolymerization, while the negative regulatory elements impede polymerization for ring formation and destabilize its lateral unions with the membrane. Information about these regulatory elements of Z ring formation and stabilization has been reviewed before (67,68). In eukaryotes, the process of cell division is highly regulated; however, in addition to tubulin, it requires regulatory elements that do not share structural nor functional homology with those of bacteria. Nonetheless, the capacity to polymerize and the GTPase activity of eukaryotic and bacterial tubulin are essential for their function and are indicative or their evolutionary conservation. Another bacterial protein that has a homolog in eukaryotic cells and is found in B. subtilis, is the cell division-related protein, DynA. In eukaryotes, dynamin is a GTPase involved in endocytosis; in this process, it assembles into a spiral around the neck of the vesicle being internalized, thus enabling its separation from the plasma membrane (42). DynA is a bacterial dynamin homolog that shares the GTPase activity and the capacity to oligomerize (33) (Fig. 1D). Table 1 resumes more common and specific characteristic of dynamin and DynA. It has been shown that DynA can mediate membrane fusion in vitro and that it acts at different stages during cell division (43). DynA is localized to the septum region and colocalizes with FtsZ, affecting Z ring formation. A bacterial dynamin and flotillin double mutant is severely affected in cell shape and motility, which suggests that these two proteins act together during cell division events. It has been proposed that DynA might facilitate membrane invagination during cell division or couple this process with Z ring formation, while flotillin helps in the recruitment of proteins necessary for cell division (33). In eukaryotic cells, several processes of endocytosis require the joint involvement of flotillin and dynamin, so that the association of these proteins in membrane remodeling processes could be considered to have a conserved evolutionary origin. Finally, we would like to mention the arrestin family of proteins, one more family of eukaryotic proteins for which a prokaryotic ancestor could be found. Arrestins are ubiquitously distributed proteins that perform a wide range of cellular activities in eukaryotic organisms, including receptor desensitization, endocytosis, signal transduction, genetic expression regulation, cellular reorganization, chemotaxis and apoptosis (69). While members of this family have low sequence identity, all of them share a highly similar tridimensional structure, conformed of two domains, namely N and C, which are separated by a polar core that stabilizes the protein in its inactive form (44). Arrestins interact with their ligand through their N domain, and they dimerize through their C domain (44). The arrestin family is divided into two categories: visual arrestins or a-arrestins and nonvisual arrestins or b-arrestins (70,71). It was previously believed that arrestins emerged after the evolutionary divergence of the first eukaryotes; however it has been reported that Spo0M, a sporulation control protein of B. subtilis (45), contains structural moieties that resemble those found in the N domain of eukaryotic visual arrestins (72). In a recent study, Sonoda et al. (46) reported the crystal structure Conserved Elements in Membrane Organization of Spo0M, demonstrating that it is highly similar to the N domain of known visual arrestins, such as the thioredoxin interacting protein (TXNIP) or the arrestin domain-containing protein 3 (ARRDC3) (Fig. 1E and Table 1). Unfortunately, there is still a lack of experimental evidence to confirm that Spo0M is a truthful ancestor of arrestin in prokaryotes; a shared origin is suggested by the conserved functionality associated to the secondary structure of this family of proteins. Conclusions Membrane remodeling processes constitute key events in all cells and require a high degree of spatiotemporal regulation. Complex regulatory mechanisms for these processes are observed in eukaryotic cells and, according to current molecular evidence, they do not appear to have arisen after the evolutionary divergence between eukaryotes and bacteria. The existence of bacterial protein homologs that participate in such regulatory events has been demonstrated, reflecting the presence of complex regulation in bacteria that had previously been ignored. Emerging technologies used in the analysis of intracellular structures, such as super resolution microscopy techniques, which are acquiring higher resolution as time goes by, will enable a highly detailed analysis of the bacterial cytoskeleton. At the same time, this should help us to identify additional regulatory elements of membrane dynamics that are evolutionarily conserved in these two domains of life, erstwhile considered to be rather different. Acknowledgements The authors thank Shirley Ainsworth for bibliographical assistance and Ricardo Ciria for computer support. This work was supported partially by CONACyT 176381 and DGAPA IN 204016. Luz Adriana Vega-Cabrera was supported by a CONACyT and DGAPA scholarship. References [1] Brocks, J. J., Logan, G. A., Buick, R., and Summons, R. E. (1999) Archean molecular fossils and the early rise of eukaryotes. Science 285, 1033–1036. [2] Cavalier-Smith, T. (1987). The origin of eukaryotic and archaebacterial cells. Ann. N Y Acad. Sci. 503, 17–54. [3] de Duve, C. (2007) The origin of eukaryotes: a reappraisal. Nat. Rev. Genet. 8, 395–403. [4] Esue, O., Cordero, M., Wirtz, D., and Tseng, Y. (2005) The assembly of MreB, a prokaryotic homolog of actin. J. Biol. Chem. 280, 2628–2635. [5] Erickson, H. P. (1995) FtsZ, a prokaryotic homolog of tubulin? Cell 80, 367– 370. [6] Lindsay, M. R., Webb, R. I., Strous, M., Jetten, M. S. M., Butler, M. K., et al. (2001) Cell compartmentalisation in planctomycetes: novel types of structural organisation for the bacterial cell. Arch. Microbiol. 175, 413–429. [7] Wagner, M., and Horn, M. (2006) The Planctomycetes, Verrucomicrobia, Chlamydiae and sister phyla comprise a superphylum with biotechnological and medical relevance. Curr. Opin. Biotechnol. 17, 241–249. [8] Fuerst, J. A., and Sagulenko, E. (2011) Beyond the bacterium: Planctomycetes challenge our concepts of microbial structure and function. Nat. Rev. Microbiol. 9, 403–413. Vega-Cabrera and Pardo-Lopez [9] Devos, D. P., and Reynaud, E. G. (2010) Intermediate steps. Science 330, 1187–1188. (80-) [10] Lee, K. C., Webb, R. I., Janssen, P. H., Sangwan, P., Romeo, T., et al. (2009) Phylum Verrucomicrobia representatives share a compartmentalized cell plan with members of bacterial phylum Planctomycetes. BMC Microbiol. 9, 5. [11] Santarella-Mellwig, R., Franke, J., Jaedicke, A., Gorjanacz, M., Bauer, U., et al. (2010) The compartmentalized bacteria of the planctomycetesverrucomicrobia-chlamydiae superphylum have membrane coat-like proteins. PLoS Biol. 8. , J. S., Kuenen, J. G., [12] Van Niftrik, L. A., Fuerst, J. A., Sinninghe Damste Jetten, M. S. M., et al. (2004) The anammoxosome: an intracytoplasmic compartment in anammox bacteria. FEMS Microbiol. Lett. 233, 7–13. [13] Pearson, A., Budin, M., and Brocks, J. J. (2003) Phylogenetic and biochemical evidence for sterol synthesis in the bacterium Gemmata obscuriglobus. Proc. Natl. Acad. Sci. USA 100, 15352–15357. [14] Kerger, B. D., Mancuso, C. A., Nichols, P. D., White D. C., Langworthy, T., et al. (1988). The budding bacteria, Pirellula and Planctomyces, with atypical 16S rRNA and absence of peptidoglycan, show eubacterial phospholipids and uniquely high proportions of long chain beta-hydroxy fatty acids in the lipopolysaccharide lipid A. Arch. Microbiol. 149, 255–260. [15] Pilhofer, M., Rappl, K., Eckl, C., Bauer, A. P., Ludwig, W., et al. (2008) Characterization and evolution of cell division and cell wall synthesis genes in the bacterial phyla Verrucomicrobia, Lentisphaerae, Chlamydiae, and Planctomycetes and phylogenetic comparison with rRNA genes. J. Bacteriol. 190, 3192–3202. [16] Lonhienne, T. G., Sagulenko, E., Webb, R. I., Lee, K.-C., Franke, J., et al. (2010) Endocytosis-like protein uptake in the bacterium Gemmata obscuriglobus. Proc. Natl. Acad. Sci. USA 107, 12883–12888. [17] Simons, K., and Ikonen, E. (1997) Functional rafts in cell membranes. Nature 387, 569–572. [18] Bramkamp, M., and Lopez, D. (2015) Exploring the existence of lipid rafts in Bacteria. Microbiol. Mol. Biol. Rev. 79, 81–100. [19] Saenz, J. P., Sezgin, E., Schwille, P., and Simons, K. (2012) Functional convergence of hopanoids and sterols in membrane ordering. Proc. Natl. Acad. Sci. USA 109, 14236–14240. [20] Matsumoto, K., Kusaka, J., Nishibori, A., and Hara, H. (2006) Lipid domains in bacterial membranes. Mol. Microbiol. 61, 1110–1117. [21] Bosak, T., Losick, R. M., and Pearson, A. (2008) A polycyclic terpenoid that alleviates oxidative stress. Proc. Natl. Acad. Sci. USA 105, 6725–6729. pez, D., and Kolter, R. (2010) Functional microdomains in bacterial mem[22] Lo branes. Genes Dev. 24, 1893–1902. [23] Kawai, F., Shoda, M., Harashima, R., Sadaie, Y., Hara, H., et al. (2004) Cardiolipin domains in Bacillus subtilis Marburg membranes. J. Bacteriol. 186, 1475–1483. [24] Mileykovskaya, E., and Dowhan, W. (2005) Role of membrane lipids in bacterial division-site selection. Curr. Opin. Microbiol. 8, 135–142. [25] Amaddii, M., Meister, M., Banning, A., Tomasovic, A., Mooz, J., et al. (2012) Flotillin-1/Reggie-2 protein plays dual role in activation of receptor-tyrosine kinase/mitogen-activated protein kinase signaling. J. Biol. Chem. 287, 7265– 7278. mez, V., Sese , M., Santamarıa, A., Martınez, J. D., Castellanos, E., et al. [26] Go (2010) Regulation of Aurora B kinase by the lipid raft protein Flotillin-1. J. Biol. Chem. 285, 20683–20690. [27] Meister, M., and Tikkanen, R. (2014) Endocytic trafficking of membranebound cargo: a flotillin point of view. Membranes (Basel) 4, 356–371. [28] Otto, G. P., and Nichols, B. J. (2011) The roles of flotillin microdomains— endocytosis and beyond. J. Cell. Sci. 124, 3933–3940. [29] Solis, G. P., Hoegg, M., Munderloh, C., Schrock, Y., Malaga-Trillo, E., et al. (2007) Reggie/flotillin proteins are organized into stable tetramers in membrane microdomains. Biochem. J. 403, 313–322. [30] Donovan, C., and Bramkamp, M. (2009) Characterization and subcellular localization of a bacterial flotillin homologue. Microbiology 155, 1786– 1799. [31] Bach, J. N., and Bramkamp, M. (2013) Flotillins functionally organize the bacterial membrane. Mol. Microbiol. 88, 1205–1217. 61 IUBMB LIFE € ller, H. M., and Graumanna, P. L. (2012) Synthetic motility [32] Dempwolff, F., Mo and cell shape defects associated with deletions of flotillin/reggie paralogs in Bacillus subtilis and interplay of these proteins with NfeD proteins. J. Bacteriol. 194, 4652–4661. [33] Dempwolff, F., Wischhusen, H. M., Specht, M., and Graumann, P. L. (2012) The deletion of bacterial dynamin and flotillin genes results in pleiotrophic effects on cell division, cell growth and in cell shape maintenance. BMC Microbiol. 12, 298. [34] Wennerberg, K., Rossman, K. L., and Der, C. J. (2005) The Ras superfamily at a glance. J. Cell. Sci. 118, 843–846. [35] Wuichet, K., and Søgaard-Andersen, L. (2014) Evolution and diversity of the ras superfamily of small GTPases in Prokaryotes. Genome Biol. Evol. 7, 57–70. € we, J. (2001) Bacterial ancestry of actin [36] Van Den Ent, F., Amos, L., and Lo and tubulin. Curr. Opin. Microbiol. 4, 634–638. [37] Hendzel, M. J. (2014) The F-act’s of nuclear actin. Curr. Opin. Cell Biol. 28, 84–89. [38] Ozyamak, E., Kollman, J. M., and Komeili, A. (2013) Bacterial actins and their diversity. Biochemistry 52, 6928–6939. [39] Eun, Y. J., Kapoor, M., Hussain, S., and Garner, E. C. (2015) Bacterial filament systems: Toward understanding their emergent behavior and cellular functions. J. Biol. Chem. 290, 17181–17189. [40] Graumann, P. L. (2007) Cytoskeletal elements in Bacteria. Annu. Rev. Microbiol. 61, 589–618. [41] Horio, T., and Murata, T. (2014) The role of dynamic instability in microtubule organization. Front. Plant Sci. 5, 1–10. [42] Praefcke, G. J. K., and Mcmahon, H. T. (2004) The Dynamin Superfamily: universal membrane tubulation and fission molecules?. Nat. Rev. Mol. Cell Biol. 5. [43] B€ urmann, F., Ebert, N., Van Baarle, S., and Bramkamp, M. (2011) A bacterial dynamin-like protein mediating nucleotide-independent membrane fusion. Mol. Microbiol. 79, 1294–1304. [44] Gurevich, V. V., and Gurevich, E. V. 2013. Structural Determinants of Arrestin Functions. The Molecular Biology of Arrestins, 1st edn. Elsevier Inc., New York, NY. [45] Han, W.-D., Kawamoto, S., Hosoya, Y., Fujita, M., Sadaie, Y., et al. (1998) A novel sporulation-control gene (spo0M) of Bacillus subtilis with a rHregulated promoter. Gene 217, 31–40. [46] Sonoda, Y., Mizutani, K., and Mikami, B. (2015) Structure of Spo0M, a sporulation-control protein from Bacillus subtilis. Acta Crystallogr. Sect. F Struct. Biol. Commun. 71, 1488–1497. [47] Kelly, L., Mezulis, S., Yates, C., Wass, M., and Sterberg, M. (2015) The Phyre2 web portal for protein modelling, prediction, and analysis. Nat. Protoc. 10, 845–858. [48] Chiba, S., Ito, K., and Akiyama, Y. (2006) The Escherichia coli plasma membrane contains two PHB (prohibitin homology) domain protein complexes of opposite orientations. Mol. Microbiol. 60, 448–457. [49] Takano, H., Hashimoto, K., Yamamoto, Y., Beppu, T., and Ueda, K. (2011) Pleiotropic effect of a null mutation in the cvn1 conservon of Streptomyces coelicolor A3(2). Gene 477, 12–18. [50] Tao, J., Han, J., Wu, H., Hu, X., Deng, J., et al. (2013) Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res. 41, 2370–2381. [51] Keilberg, D., and Søgaard-Andersen, L. (2014) Regulation of bacterial cell polarity by small GTPases. Biochemistry 53, 1899–1907. 62 [52] Dong, J. H., Wen, J. F., and Tian, H. F. (2007) Homologs of eukaryotic Ras superfamily proteins in prokaryotes and their novel phylogenetic correlation with their eukaryotic analogs. Gene 396, 116–124. ceres, R., Abou-Ghali, M., and Plastino, J. (2015) Reconstituting the actin [53] Ca cytoskeleton at or near surfaces in vitro. Biochim. Biophys. Acta-Mol. Cell Res. 1853, 3006–3014. € rmann, F., and Hamoen, L. W. (2014) The actin homologue [54] Strahl, H., Bu MreB organizes the bacterial cell membrane. Nat. Commun. 5, 1–11. pez, R., and Errington, J. (2001) Control of cell [55] Jones, L. J. F., Carballido-Lo shape in bacteria: Helical, actin-like filaments in Bacillus subtilis. Cell 104, 913–922. [56] Mayer, M. P., and Bukau, B. (2005) Hsp70 chaperones: cellular functions and molecular mechanism. Cell. Mol. Life Sci. 62, 670–684. [57] Pichoff, S., and Lutkenhaus, J. (2005) Tethering the Z ring to the membrane through a conserved membrane targeting sequence in FtsA. Mol. Microbiol. 55, 1722–1734. € we, J. (2012) FtsA forms [58] Szwedziak, P., Wang, Q., Freund, S. M. V., and Lo actin-like protofilaments. EMBO J. 31, 2249–2260. € we, J. (2001) Prokaryotic origin of the actin [59] Van den Ent, F., Amos, L. A., Lo cytoskeleton. Nature 413, 39–44. € pez, R., and Errington, J. (2003) The bacterial cytoskeleton: in [60] Carballido-Lo vivo dynamics of the actin-like protein Mbl of Bacillus subtilis. Dev. Cell 4, 19–28. [61] Carballido-Lopez, R. (2006) The bacterial actin-like cytoskeleton. Microbiol. Mol. Biol. Rev. 70, 888–909. [62] Egan, A. J. F., Biboy, J., van’t Veer, I., Breukink, E., and Vollmer, W. (2015) Activities and regulation of peptidoglycan synthases. Philos. Trans. R. Soc. B Biol. Sci. 370, 20150031. [63] Machta, B. B., Papanikolaou, S., Sethna, J. P., and Veatch, S. L. (2011) Minimal model of plasma membrane heterogeneity requires coupling cortical actin to criticality. Biophys. J. 100, 1668–1677. [64] Chichili, G. R., and Rodgers, ÆW. (2009) Cytoskeleton–membrane interactions in membrane raft structure. Cell. Mol. Life Sci. 66, 2319–2328. mez-Llobregat, J., Buceta, J., and Reigada, R. (2013) Interplay of cytoskel[65] Go etal activity and lipid phase stability in dynamic protein recruitment and clustering. Sci. Rep. 3, 2608. € we, J., and Amos, L. A. (1998) Crystal structure of the bacterial cell[66] Lo division protein FtsZ. Nature 391, 203–206. [67] Adams, D. W., and Errington, J. (2009) Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat. Rev. Microbiol. 7, 642– 653. [68] Lutkenhaus, J., Pichoff, S., and Du, S. (2012) Bacterial cytokinesis: from Z ring to divisome. Cytoskeleton 69, 778–790. [69] Xiao, K., McClatchy, D. B., Shukla, A. K., Zhao, Y., Chen, M., et al. (2007) Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proc. Natl. Acad. Sci. USA 104, 12011–12016. [70] Patwari, P., and Lee, R. T. (2012) An expanded family of arrestins regulate metabolism. Trends Endocrinol. Metab. 23, 216–222. [71] Gurevich, V. V., Hanson, S. M., Song, X., Vishnivetskiy, S. A., and Gurevich, E. V. (2011) The functional cycle of visual arrestins in photoreceptor cells. Prog. Retin. Eye Res. 30, 405–430. [72] Alvarez, C. E. (2008) On the origins of arrestin and rhodopsin. BMC Evol. Biol. 8, 222. Conserved Elements in Membrane Organization