Moonlighting Motors: Kinesin, Dynein, and Cell Polarity - PubMed (original) (raw)
Review
Moonlighting Motors: Kinesin, Dynein, and Cell Polarity
Wen Lu et al. Trends Cell Biol. 2017 Jul.
Abstract
In addition to their well-known role in transporting cargoes in the cytoplasm, microtubule motors organize their own tracks - the microtubules. While this function is mostly studied in the context of cell division, it is essential for microtubule organization and generation of cell polarity in interphase cells. Kinesin-1, the most abundant microtubule motor, plays a role in the initial formation of neurites. This review describes the mechanism of kinesin-1-driven microtubule sliding and discusses its biological significance in neurons. Recent studies describing the interplay between kinesin-1 and cytoplasmic dynein in the translocation of microtubules are discussed. In addition, we evaluate recent work exploring the developmental regulation of microtubule sliding during axonal outgrowth and regeneration. Collectively, the discussed works suggest that sliding of interphase microtubules by motors is a novel force-generating mechanism that reorganizes the cytoskeleton and drives shape change and polarization.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Figures
Figure 1. Highly conserved C-terminal microtubule binding site of kinesin-1 heavy chain
Amino acids of kinesin-1 heavy chain C-terminal region from 11 species are aligned in Clustal Omega (
http://www.ebi.ac.uk/Tools/msa/clustalo/
) using the following kinesin heavy chain protein sequences: Caenorhabditis elegans, Drosophila melanogaster, Aplysia californica, Doryteuthis pealeii (squid), Strongylocentrotus purpuratus (sea urchin), Danio rerio (zebrafish), Xenopus tropicalis, Gallus gallus (chick), Rattus norvegicus (rat), Mus musculus (mouse) and Homo sapiens (KIF5A, KIF5B, and KIF5C). ATP-independent microtubule binding site is highlighted in the light blue box, and all basic residues in the microtubule binding site are labeled in red.
Figure 2. Microtubule sliding by kinesin-1 requires antiparallel orientation
Kinesin-1 non-cooperative binding to two microtubules using its motor domain and C-terminal microtubule binding site leads to sliding of antiparallel microtubules (A) and bundling of parallel microtubules (B).
Figure 3. Visualization of microtubule sliding in Drosophila neurons using photoconvertible tubulin
(A) A spherical-shaped young neuron expressing photoconvertible EOS-tagged α-tubulin. (B) 400nm light is applied to a restricted area to photoconvert a subset of microtubules in the young neurons. (C) A subset of microtubules is photoconverted from green to red. (D) Red microtubule fragments are scattered throughout the cell body and in the newly formed neurites by microtubule-microtubule sliding, revealed by time-lapse movies.
Figure 4. A model of microtubule motors driving microtubule sliding at different stages
Kinesin-1 drives anti-parallel microtubules sliding apart in early-stage neurons, inducing the formation of initial neurites in spherical-shaped young neurons (left panel). At later stages, cytoplasmic dynein anchors at cell cortex by interacting with F-actin and sorts out the microtubules of wrong orientation (minus-ends out), and slides microtubules of right orientation (plus-ends out) towards the growth cone to counteract actin retrograde flow driven by myosins (right panel). Both kinesin-driven and dynein-driven microtubule sliding can be regulated by microtubule crosslinker(s).
References
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