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Shinsuke Niwa

Publications and source records attributed to Shinsuke Niwa.

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Physical parameters describing neuronal cargo transport by kinesin UNC-104

In this review, we focus on the kinesin-3 family molecular motor protein UNC-104 and its regulatory protein ARL-8. UNC-104, originally identified in Caenorhabditis elegans (C. elegans), has a primary role transporting synaptic vesicle precursors (SVPs). Although in vitro single-molecule experiments have been performed to primarily investigate the kinesin motor domain, these have not addressed the in vivo reality of the existence of regulatory proteins, such as ARL-8, that control kinesin attachment to/detachment from cargo vesicles, which is essential to the overall transport efficiency of cargo vesicles. To quantitatively understand the role of the regulatory protein, we review the in vivo physical parameters of UNC-104-mediated SVP transport, including force, velocity, run length and run time, derived from wild-type and arl-8-deletion mutant C. elegans. Our future aim is to facilitate the construction of a consensus physical model to connect SVP transport with pathologies related to deficient synapse construction caused by the deficient UNC-104 regulation. We hope that the physical parameters of SVP transport summarized in this review become a useful guide for the development of such model.

physics.bio-ph

Non-invasive force measurement reveals the number of active kinesins on a synaptic vesicle precursor in axonal transport regulated by ARL-8

Kinesin superfamily protein UNC-104, a member of the kinesin-3 family, transports synaptic vesicle precursors (SVPs). In this study, the number of active UNC-104 molecules hauling a single SVP in axons in the worm Caenorhabditis elegans was counted by applying a newly developed non-invasive force measurement technique. The distribution of the force acting on a SVP transported by UNC-104 was spread out over several clusters, implying the presence of several force-producing units (FPUs). We then compared the number of FPUs in the wild-type worms with that in arl-8 gene-deletion mutant worms. ARL-8 is a SVP-bound arf-like small guanosine triphosphatase, and is known to promote unlocking of the autoinhibition of the motor, which is critical for avoiding unnecessary consumption of adenosine triphosphate when the motor does not bind to a SVP. There were fewer FPUs in the arl-8 mutant worms. This finding indicates that a lack of ARL-8 decreased the number of active UNC-104 motors, which then led to a decrease in the number of motors responsible for SVP transport.

physics.bio-ph