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Transcript
Lecture 16 Outline
The Cytoskeleton
Composed of a Network of Protein Fibers Extending throughout the Cytoplasm. Three
Major Roles: 1. Provides Mechanical Strength 2. Controls Cell Shape 3. Drives and
Guides Movement. Three Major Components: 1. Actin 2) Microtubules 3) Intermediate
Actin (Microfilaments) Two intertwined strands of actin, each a polymer of actin
subunits. Linear Form: Twisted double chain of actin. Form higher ordered structure
including Structural Networks or Bundles: Form as result of Accessory proteins. Major
Functions in Maintenance of Cell Shape (tension bearing elements)changes in Cell
Shape, Muscle Contraction, Cell Motility (Pseudopodia), Cell Division (Cleavage Furrow
Formation) Actin Filaments have polarity, bind ATP, hydrolysis reduces affinity of
monomers for each other- reducing polymer stability ( much like MT) Accessory proteins
play key role in Actin filament formation and whether networks or bundles, etc. Drugs
can influence assembly/disassembly of actin.
Microtubules (MTs) Structure: Hollow Tubes (Rods) consist of 13 Protofilaments
composed of Tubulin. Protofilaments are long linear strings of subunits joined end to end.
Rod has 25 nm Diameter Cross Section. The Protein Subunits are composed of globular
protein, Tubulin. Exist as an alpha-tubulin and beta tubulin heterodimer. Main functions
include Internal Scaffolding for Support - Resist Compressive and Bending Forces
Movement of Organelles- including vesicular transport from Golgi to Plasma Membrane,
are the Motile Elements of Cilia and Flagella and are critical for mitosis, dissemble and
reassemble into mitotic spindle. Roles in Maintaining of Internal Cell Organization and
Cell Shape. Formation of Tubulin Filaments- Depends on tubulin dimer concentration
High concentrations lead to growth or assemble, while Low concentrations lead to
disassembly or depolymerization. Above Critical concentration (concentration of free
tubulin dimers) assembly will occur, below- disassembly occurs
Microtubules exhibit dynamic instability- a result of capacity to bind and hydrolyze GTP.
GTP cap present on + end, that is tubulin-GTP bound form, provided addition continues
always some at end. Not enough GTP tubulin available, GTP is being hydrolyzed and if
assembly slows, now loses GTP cap- rapid shortening of MT.
Drugs and MAPS (Microtubule Associated Proteins) can influence rate of assembly/
disassembly. Microtubules nucleate at MTOCs – centrosome is main one of animal cells.
Gamma tubulin present in rings- sites for MT assembly. Serves several functions
including anchoring minus end, orienting filament, regulating number of filaments, etc.
Centrioles are also present in Centrosome. They are composed of MT cylinders; organize
centrosome, no role in nucleation
Intermediate Filaments (IMFs) : Limited to vertebrates and some other organisms
lacking skeleton. Monomers of Elongated and fibrous proteins form coiled coil dimers
that then assemble with another dimer in antiparallel and staggered fashion. Eight
tetramers come together to form thick rope like cables with diameter of 8-12 nm
(intermediate in size relative to actin and microtubules- hence the name). Unlike, MTs
and MFs, IMFs lack structural polarity and do not function with motor proteins (except as
cargo), do not require nucleotides for assembly. While dynamic, primarily more stable
structures than MTs and MFs. IMFs include nuclear lamins that function to form nuclear
lamina that strengthen and supports nuclear envelope and provide attachment sites for
chromosomes and nuclear pores. Other IFs include Keratin, Vimentin and
Neurofilaments. Cytoplasmic filaments like keratin function to anchor nucleus and other
organelles. Function in maintenance of cell shape and prevention damage by stress.
Keratin of Adjacent epithelial cells attach to large plaques called Desmosomes, critical
for cells to withstand stress. Mutation of keratins can lead to blistering of skin, due to loss
of ability to withstand stress.
Next time more detail regarding associated proteins and regulation of various kinds of
cell motility.