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main functions of the cytoskeleton
maintain cell shape, organization, and support internal and external environment
three classes of cytoskeletal filaments
microfilaments (actin), microtubules, and intermediate filaments (vertebrae)
what is microtubule nucleation
slow formation of a stable seed from tubulin dimers and protofilaments
what is a microtubule dynamic instability
microtubules repeatedly switch between growth and shrinkage
what protein complex helps nucleate microtubules
y-tubulin ring complex (y-TuRC)
where are microtubules commonly nucleated
MTOCs enriched in y-tubulin
main MTOC in many animal cells
centrosome
what is the centrosome made of
two centrioles surrounded by pericentriolar material (PCM)
where is y-tubulin concentrated in many nondividing animal cells
at the centrosome
what do microtubule-associated proteins (MAPs) do
bind microtubules and regulate their stability and organization
what do MAP2 and Tau do
help stabilize and organize microtubules and influence bundle spacing
how is Tau associated with neurodegenerative disease
abnormal Tay can from aggregates
Tau mutations can cause some neurodegenerative diseases
how do microtubule orientations differ in axons and dendrites
axons: most uniform, plus ends outwards
dendrites: mixed orientations
what are the two major microtubule motor proteins
kinesin usually moves toward + ends
cytoplasmic dynein moves toward - ends
what is conventional kinesin made of + what do it head and tail do
2 heavy chains, 2 light chains
heads use ATP for movement
tail region binds cargo
how does kinesin travel long distances along microtubules
its two heads take regular 8nm steps, usually keeping at least one head attached
what feature is shared by proteins in the kinesin superfamily
a related motor domain that binds microtubules and uses ATP
function of kinesin-13
depolymerizes both microtubule ends; regulates spindle assembly
doesn’t walk along tracks
direction kinesin-14 (Ncd) move
toward (-)
how does kinesin-14 organize microtubule bundles
its tail bind microtubules, helping crosslink and organize them
how does cytoplasmic dynein move
takes large, irregular steps toward the microtubule minus end
what do microtubule motors do in the secretory pathway
transport vesicles between organelles and toward cellular destinations
what are melanosomes and how do they move
organelles that make/store melanin
kinesin and dynein move them on microtubules
how can an axonal vesicles move in both directions
it can carry kinesin and dynein; regulating their activity controls transport direction
how can kinesin be inhibited to favor minus-end transport
kinesin-binding protein (KBP) can prevent certain kinesins from binding microtubules
how do motile cilia and flagella differ
cilia usually beat with power and recovery strokes
flagella often move in waves
what is the axoneme
the microtubule-based core of cilia and flagella often w/ a 9+2 arrangement
how does axonemal dynein move cilia and flagella
uses ATP to slide adjacent microtubule doublets; constraints convert sliding into bending
What is G-actin, and what nucleotide does it carry?
Globular actin: a single protein subunit that binds ATP or ADP.
What gives F-actin polarity? What are G-actin and F-actin?
Uniform subunit orientation. G-actin = monomer; F-actin = polarized filament with + and − ends.
At which end do actin filaments grow fastest?
The plus (+), or barbed, end.
What does phalloidin do to actin filaments?
Binds and stabilizes F-actin, preventing depolymerization.
What do capping proteins do?
Bind filament ends; plus-end capping protein blocks actin addition and loss. It is a heterodimer.
What does cofilin do to actin filaments?
Binds older ADP-actin, changes filament twist, and promotes severing and disassembly.
What two protrusions do migrating cells form?
Filopodia (thin fingers) and lamellipodia (broad sheets).
How is actin organized in filopodia versus lamellipodia?
Filopodia contain parallel bundles; lamellipodia contain branched actin networks.
What is α-actinin, and what does it do?
A relatively rigid dimeric crosslinker that connects actin filaments into bundles.
What is filamin, and why is it flexible?
A flexible dimeric crosslinker that joins actin filaments at different angles.
How does the Arp2/3 complex form actin branches?
Its 7 subunits bind a filament's side and nucleate a new branch using actin monomers.
Where are many F-actin structures attached?
To the plasma membrane through actin-binding linker proteins.
What are ERM proteins, and how is ezrin activated?
Ezrin, radixin, moesin link actin to membranes. Ezrin phosphorylation helps expose binding sites.
How do cells build different actin structures?
By changing the activity and location of actin-binding proteins.
What are the three major Rho GTPases and their ON/OFF states?
Cdc42, Rac, Rho. GTP-bound = ON; GDP-bound = OFF.
How do Rho GTPases control actin structures?
Coordinate actin regulators: Cdc42 → filopodia; Rac → lamellipodia; Rho → stress fibres.
Why do Rho GTPases activate proteins locally?
To build specific actin structures only where the cell needs them.
What do all myosins share, and how do they differ?What do all myosins share, and how do they differ?
Similar motor domains but diverse C-terminal tails; conventional and unconventional types.
What happens in an actin-sliding assay?
Myosin fixed to glass uses ATP to move fluorescent actin filaments across the surface.
What does myosin V do, and which direction does it move?
Transports and tethers organelles; walks toward the actin plus (+) end.
What is the function of myosin I?
A single-headed motor that binds membranes and actin to generate membrane deformation.