Post on 21-Dec-2015
The cytoskeleton
• Gives the cell its shape
• Allows the cell to organize its components
• Produces large-scale movements (I.e. muscle contraction, cell crawling, propulsion via cilia and flagella)
What do microtubules do?
• Establish an internal polarity to movements and structures in the interphase cell
• Participate in chromosome segregation during cell division
• Establish cell polarity during cellular movement
• Produce extracellular movement via beating of cilia and flagella
Microtubules exhibit a behavior termed dynamic instability
• Total mass of polymerized tubulin remains constant, but individual microtubules are dynamic
• Growth: assembly of microtubule
• Shrinkage: disassembly of microtubule
• Catastrophe: switching from growth to shrinking
• Rescue: switching from shrinking to growth
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Microtubule-associated proteins
• MAPs can function as cross-bridges connecting microtubules.
• They can affect microtubule rigidity and assembly rate.
Centrosomes act to polarize the microtubule network
• Plus end - fast growing, usually in the cytoplasm
• Minus end - slow growing, anchored at the centrosome in most cells
Why are microtubules dynamic?
• Microtubule dynamics allow the cell to quickly reorganize the network when building a mitotic spindle
• Dynamics also allow microtubules to probe the cytoplasm for specific objects and sites on the plasma membrane - search and capture
Motor proteins
• Enzymes that convert ATP hydrolysis directly into movement along cytoskeletal filaments
• Some motors move towards the plus end, others move to the minus end
• Carry cargo (organelles, protein complexes, RNA) and mediate microtubule/microtubule sliding
First evidence of microtubule motors came from study of axonal transport
Extruded axoplasm assays - Cytosolis squeezed from the axon with aroller onto a glass coverslip.
Addition of ATP shows movementby videomicroscopy
Vesicle movement in this systemis about 1-2um/s similar to fast axonaltransport.
There are two families of microtubule motors
• Kinesins– Move cargo to the plus
end– In mitosis, participate in
mitotic spindle dynamics– Usually dimers of 2
heavy chains and 2 light chains
• Dyneins– Move cargo to the minus
end– In mitosis, participate in
mitotic spindle dynamics– Power beating of cilia
and flagella– Large protein complex
with many subunits
Structure of kinesin
• 2 heavy chains + 2 light chains
• Microtubule and ATP binding sites in the head
• Cargo-binding site in the tail and light chains
Kinesin “walks” along microtubules
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There are two classes of dyneins
• Cytoplasmic dynein– Carries cargo in the
cytoplasm– Involved in mitotic
spindle dynamics
• Axonemal dyneins– Localized exclusively in
cilia and flagella– The motors that power
cilliary and flagellar beating
Cilia and flagella
• Cilia line the epithelial tissue of the respiratory tract to sweep particulate matter out of the airways
• Cilia line the oviduct to push the egg
• Non-motile cilia detect signals
• Flagella allow sperm to swim
• Flagella are essential for left-right asymmetry during development (Kartagener syndrome: situs inversus, sinusitis, brochiectasis)
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Cilia in the respiratory tract
Mutations that disrupt cilia cause multiple diseases
• Fertility (sperm motility, ectopic pregnancy)
• Polycystic kidney disease
• Respiratory infection
• Retinal degeneration
• Hearing/balance loss (Usher syndrome)
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