Number Dependence of Microtubule Collective Transport by Kinesin and Dynein

Abstract

Translational motors that depend on cytoskeletal elements,
either actin or tubulin, for their activity are critical for cellular function in
eukaryotes. Microtubule (MT)-dependent motors are broadly classified
as dyneins and kinesins, based on sequence similarity. Typically,
dyneins walk towards the minus-ends of MTs, while kinesins walk
towards the plus-ends, with some plant and animal kinesins also seen to
be minus-end directed. While our understanding of motor mechanics at
a single-molecule level has rapidly improved due to developments in
force spectroscopy, in vivo motor transport often involves multiple motors
acting together. Here, we review our current understanding of collective
effects that emerge in motor-driven transport in vivo based on physical
mechanisms inferred from in vitro reconstitution experiments involving
MT transport, or ‘gliding assays’. We discuss the evidence for number
dependence in cargo transport at MT cross-overs, orientation sorting of
MTs during axonal regeneration in neurons, spindle bipolarization by MT
transport, and nuclear positioning during mitosis in the model yeasts
Saccharomyces cerevisiae and Schizosaccharomyces pombe. We discuss
how minimal in vitro gliding assays have been successfully used to
identify the mechanical properties of collective motor transport that produce
such cooperative effects. The ‘loose coupling’ mechanism of
Oosawa, which was developed to explain the emergence of cooperation
in collective motor transport, appears to be consistent with evidence
from kinesin, but not dynein. Additionally, substrate rigidity also appears
to play a role in collective force generation, as seen in lipid-anchorage
studies of collective transport. Thus, a deeper understanding of the intraand
inter-motor properties of kinesins and dyneins, as well as non-motor
effects due to the substrate is required, for the emergence of a complete
picture of the in vivo mechanobiology of collective motor transport.