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.
KeywordsMotor proteins Kinesin Cellular cargo transport Neuronal disease
We thank the participants of the Asian Biophysics Association (ABA) Symposium 2018 for comments on the study.
Compliance with ethical standards
This work was supported by JST PRESTO (grant number JPMJPR1877), AMED PRIME (grant number JP18gm5810009), and JSPS KAKENHI (grant number 17H03659) to K. H., as well as JSPS KAKENHI (grant number 17H05010) to S. N.
Conflict of interest
We declare that there are no conflicts of interest.
All the animal experiments were conducted in compliance with protocols which were approved by the Institutional Animal Care and Use Committee, Tohoku University.
- Ciliberto S, Joubaud S, Petrosyan A (2010) Fluctuations in out-of-equilibrium systems: from theory to experiment J Stat Mech-Theory E:P12003 doi:Artn P12003. 10.1088/1742-5468/2010/12/P12003Google Scholar
- Encalada SE, Goldstein LS (2014) Biophysical challenges to axonal transport: motor-cargo deficiencies and neurodegeneration. Annu Rev Biophys 43:141–169. https://doi.org/10.1146/annurev-biophys-051013-022746 CrossRefGoogle Scholar
- Gross SP (2004) Hither and yon: a review of bi-directional microtubule-based transport. Phys Biol 1:R1–R11. https://doi.org/10.1088/1478-3967/1/2/R01
- Hayashi K, Tsuchizawa Y, Iwaki M, Okada Y (2018b) Application of the fluctuation theorem for non-invasive force measurement in living neuronal axons. Mol Biol Cell: mbcE18010022. https://doi.org/10.1091/mbc.E18-01-0022
- Kanada R, Sasaki K (2013) Energetics of the single-headed kinesin KIF1A physical review E, statistical, nonlinear, and soft matter physics. 88:022711. https://doi.org/10.1103/PhysRevE.88.022711
- Niwa S (2017) Immobilization of Caenorhabditis elegans to analyze intracellular transport in neurons. J Vis Exp. https://doi.org/10.3791/56690
- Peskin CS, Oster G (1995) Coordinated hydrolysis explains the mechanical behavior of kinesin. Biophys J 68:202S–210S discussion 210S-211SGoogle Scholar