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#microtubule

3 public questions tagged with this topic.

Cytoskeleton

What is the primary function of dynein in cellular transport?

Cellular cargo movement includes vesicular trafficking but cilia and flagella beating demands distinct high power motors specialized for sliding instead of cargo carrying. Axonemal dynein evolved from cytoplasmic dynein forms large arrays of outer and inner dynein arms repeating every 96 nm along A tubule of axonemal doublet in nine fold symmetric axoneme. Each arm hydrolyzes ATP in AAA1 to AAA4 rings transmitting conformational change through stalk causing sliding of adjacent B tubule toward base at velocities up to 5 microns per second. Because axoneme constrained by radial spokes linking doublets to central pair and nexin dynein regulatory complex crosslinking doublets sliding converted into bending propagated as waves driving fluid propulsion. Cytoplasmic dynein transports vesicles toward minus ends transport toward plus ends performed by kinesin severing done by katanin. Thus major force for cilia and flagella movement originates from axonemal dynein essential for mucociliary clearance reproduction and left right asymmetry establishment during development.

Ref: Ishikawa, Curr Biol – Dynein generates force for cilia flagella movement via axonemal arms.

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Cytoskeleton

Which motor protein moves cargo towards the (+) end of microtubules?

Long distance intracellular transport along microtubules employs directional motors whose motor domains read polarity via asymmetric binding and neck linker orientation. Majority of kinesin superfamily members possess N terminal motor domains that exhibit plus end directed motility via neck linker docking mechanism: ATP binding induces neck linker zippering toward plus end swinging trailing head forward 8 nm. Kinesin-1 KIF5B exemplifies conventional plus motor ferrying mitochondria synaptic vesicle precursors lysosomes and mRNP anterogradely toward cell periphery or axon terminals at about 1 micron per second. Dynein is obligate minus end directed motor moving cargo toward centrosome and nucleus for degradation. Myosin II operates on actin filaments for contractility not microtubules. Kinesin-14 family such as NCD and HSET moves minus end due to C terminal motor domain inverted orientation. Hence kinesin-1 epitomizes plus end cargo transport underlying polarized distribution peripheral positioning and axonal anterograde traffic essential for synaptic function and organelle inheritance during division.

Ref: Vale, Cell 2003 – Kinesin family plus end motility; Alberts Chapter 16 Kinesin-1 transport role.

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Cell Cycle Regulation

What is the correct type of attachment between chromosomes and microtubules?

Kinetochore-microtubule interactions evolve through search and capture mechanism mediated by dynamic microtubule instability. Successful biorientation defined as amphitelic configuration where sister kinetochores attached to microtubules originating from opposite spindle poles. This arrangement produces pulling forces toward poles resisted by centromeric cohesin complex linking sisters, generating inter-kinetochore tension about 0.5 to 1 micron stretch detectable as separation between CENP-A foci. Tension acts as stabilization signal and silences spindle checkpoint. By contrast monotelic state where single sister attached leaves other unattached signaling MCC production, syntelic where both sisters attach same pole lacks inter-sister tension causing Aurora B dependent destabilization, and merotelic where single kinetochore captures microtubules from both poles creates lagging chromosome because tension partly satisfied but attachment merotelically bridging both poles; if uncorrected leads to aneuploidy. Merotelic errors particularly common and require Aurora B and MCAK for resolution. Achievement of amphitelic attachment for all chromosomes manifests as congression to equatorial metaphase plate, fulfilling condition for APC/C-Cdc20 activation and securin degradation. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.

Ref: Cimini, Merotelic Attachment and Chromosome Missegregation, Curr Biol 2008; Alberts et al., Molecular Biology of the Cell, Chapter 17, Chromosome Alignment.

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