5: Cytoskeleton Flashcards
General features
- cytoskeletal elements are not membrane bound
- all cytoskeletal elements are polymers
- MT= polymers of tubulin
- MF = polymers of actin
- IF = variable
- all non-covenant linkages
- i.e. dynamic elements
Microtubules
- largest fibres (25nm)
- hollow tubes made of tubulin proteins
- a-tubulin + b-tubulin = heterodimers
- heterodimers —> protofilaments
- 13 protofilaments —> microtubule
-MT are POLAR
+ end (B-subunit) is where it grows (may have GTP or GDP cap)
- end (a-subunit) only has GTP cap
- both a and B can bind GTP
- B subunit can hydrolyze GTP to GDP
- a subunit ALWAYS has GTP
Microtubule associated proteins
- structural MAPs
- increase stability of microtubules and promote assembly
-eg. MAP1, MAP2, MAP4, tau
Tau
- stabilize MTS
- if mutated or hyperphosphorylated MTS become unstable, tangled climbs
- associated with frontotemporal dementia
Dynamic instability model
- if there is a GTP cap, more aB dimers will join and MT will grow
- eventually GTP will be hydrolyzed
- if there is a low concentration of tubulin dimers in the cell, the GTP cap will disappear
- without GTP it is unstable and will disassemble leading to MT shrinkage (catastrophe)
Microtubule organizing centres
- microtubules grow out of MTOCs
- nucleation = initiation of growth
- eg. Centrosome
Centrosome
- composed of 2 centrioles
- each centriole is made up of 9 tripled MTS plus pericentriolar material (PCM)
Pericentriolar matrix
- PCM is critical for microtubule nucleation
- gamma tubulin present in PCM
- gamma tubulin ring complex forms a base from which the microtubule can grow
Microfilaments
- smallest fibres (6-8nm)
- made of actin
- important for movement (within cell and cell itself)
Microfilaments functions
- Cell shape
- Cell migration
- Transport of vesicles and organelles
- Cytokinesis
- Muscle contraction
Microfilament structure
- made of actin
- G-actin=globular actin (monomers)
- F-actin=filamentous actin (polymer/microfilament)
- G-actin binds ATP which is later hydrolyzed to ADP
- within a filament the actin monomers are oriented in the same direction
- filament is POLAR
Myosin
- accessory protein for microfilaments
- attaches to filament
- had a head and neck
- S1 fragment sticks out to form “barbed wire” appearance
Polarity of actin
- pointed end = minus end
- barbed end = plus end
- growth occurs at PLUS end
Actin formation
- acting can be organized in bundles
- parallel assembly of filaments closely together
- often found in filopodia
- actin can be organized in networks
- meshwork of perpendicular fibres
- often found in lemllipodium
-microfilament organization is mediated by actin-binding proteins
Actin binding proteins
- Proteins that regulate monomers and their polymerization
- Proteins that cap the ends
- Proteins that crosslink or bundle filament
- Proteins that sever microfilaments
- Proteins that link actin to membranes
- Proteins that promote branching
Proteins that regulate monomers and their polymerization
- Thymosin B4
- controls amound of G-actin available for polymerization
- profilin
- adds ATP to monomers to increase filament growth rate
Proteins that cap the ends
-a cap will prevent further addition or loss of subunits
- CapZ caps PLUS end
- no monomers can be added
- Tropomodulin caps MINUS end
- no monomers can fall off
Proteins that crosslink or bundle filaments
- attach to more that 1 protein at a time
- holds filaments together
- Filamin
- holds filaments at right angles
- villin
- holds filaments parallel