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Cell and Molecular Biology
Cytoskeleton-1
Behrouz Mahmoudi
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The cytoskeleton
Is a dynamic 3-dimensional structure that fills the cytoplasm, and is present in both
eukaryotic and prokaryotic cells. The cytoskeleton acts as both muscle and skeleton, and
plays a role in cell protection, cell motility (migration), cytokinesis, intracellular transport,
cell division and the organization of the organelles within the cell
Cytoskeleton has three main structural components:
microfilaments, intermediate filaments, and microtubules.
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Actin filaments (also called microfilaments)
Monomers of the protein actin polymerize to form long, thin fibers that are about 8 nm in
diameter.
Functions:
provide mechanical strength to the cell
link transmembrane and cytoplasmic proteins
anchor centrosomes during mitosis
generate locomotion in cells
interact with myosin to provide the force of muscular contraction
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Protein folding
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Microfilaments are solid rods made of a protein known as actin
When it is first produced by the cell, actin appears in a globular form
(G-actin) creating a filamentous form of the protein (F-actin)
Each microfilament exhibits polarity, the two ends of the filament being distinctly
different. This polarity affects the growth rate of microfilaments, one end (termed the
plus end) typically assembling and disassembling faster than the other (the minus end)
Actin can hydrolyze its bound ATP to ADP + Pi, releasing Pi. The actin monomer can
exchange bound ADP for ATP. The conformation of actin is different, depending on
whether there is ATP or ADP in the nucleotide-binding site
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G-actin (globular actin) with bound ATP can polymerize, to form Factin (filamentous actin).
F-actin may hydrolyze its bound ATP to ADP + Pi and release Pi. ADP release from the
filament does not occur because the cleft opening is blocked.
ADP/ATP exchange: G-actin can release ADP and bind ATP, which is usually present in
the cytosol at higher concentration than ADP
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Filament growth at one end, designated plus (+), exceeded that at the
other end, designated minus (-). In electron micrographs, bound myosin
heads appear as arrowheads pointing toward the negative end of the
filament.
Actin filaments may undergo treadmilling, in which filament length remains approximately
constant, while actin monomers add at the (+) end and dissociate from the (-) end. This
has been monitored using brief exposure to labeled actin monomers (pulse labeling)
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Actin filament nucleation
The initial step in the formation of an actin filament, in which actin
monomers combine to form a new filament. Nucleation is slow relative to
the subsequent addition of more monomers to extend the filament
three main classes of protein have been
identified that bypass the need for
spontaneous nucleation and promote the
initiation of new filament assembly.
Nucleators: are the actin-related protein-2/3
(ARP2/3) complex, spire and formins.
Branched actin filaments are observed in
most organelles, and specific NPFs, such
as WASP, N-WASP, WAVEs, WASH, and
WHAMM, exist for each organelle.
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Treadmilling of actin filaments can be altered by profilin and ADF which
generally increase and decrease the size of actin filaments, respectively.
Capping proteins:
bind at the ends of actin filaments. Different capping proteins may either stabilize an
actin filament or promote disassembly. They may have a role in determining
filament length. For example:
Tropomodulins cap the minus end, preventing dissociation of actin monomers.
CapZ capping protein binds to the plus end, inhibiting polymerization. If actin monomers
continue to dissociate from the minus end, the actin filament will shrink.
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Cross-linking proteins:
organize actin filaments
into
bundles
or
networks. Actin-binding
domains of several of
the
cross-linking
proteins (e.g., filamin,
a-actinin,
spectrin,
dystrophin and fimbrin)
are homologous.
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Some actin-binding proteins such as a-actinin, villin and fimbrin bind
actin filaments into parallel bundles. Depending on the length of a crosslinking protein, or the distance between actin-binding domains, actin
filaments in parallel bundles may be held close together, or may be far
enough apart to allow interaction with other proteins such as myosin
Filamins:
Dimerize, through antiparallel association
of their C-terminal domains, to form Vshaped cross-linking proteins that have a
flexible shape due to hinge regions.
Filamins organize actin filaments into
loose networks that give some areas of
the cytosol a gel-like consistency.
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FilGAP is a newly recognized filamin A (FLNa)-binding RhoGTPaseactivating protein.
to control actin remodeling.
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Spectrin:
Is an actin-binding protein that forms an elongated tetrameric complex
having an actin-binding domain at each end. With short actin filaments,
spectrin forms a cytoskeletal network on the cytosolic surface of the
plasma membrane of erythrocytes and some other cells.
Ankyrins are a family of adaptor proteins that mediate the attachment of integral
membrane proteins to the spectrin-actin based membrane cytoskeleton
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