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 intra- and 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.