F-box protein FBXB-65 regulates anterograde transport of the kinesin-3 motor UNC-104 through a PTM near its cargo-binding PH domain.

Autor:	Sabharwal V; Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India., Boyanapalli SPP; Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India., Shee A; Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005, India.; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India.; Northwestern Institute on Complex Systems and ESAM, Northwestern University, Evanston, IL 60208, USA., Nonet ML; Department of Neuroscience, Washington University School of Medicine, St Louis, MO 63110, USA., Nandi A; Department of Physics, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India., Chaudhuri D; Institute of Physics, Sachivalaya Marg, Bhubaneswar 751005, India.; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India., Koushika SP; Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2024 Apr 01; Vol. 137 (7). Date of Electronic Publication: 2024 Apr 16.
DOI:	10.1242/jcs.261553
Abstrakt:	Axonal transport in neurons is essential for cargo movement between the cell body and synapses. Caenorhabditis elegans UNC-104 and its homolog KIF1A are kinesin-3 motors that anterogradely transport precursors of synaptic vesicles (pre-SVs) and are degraded at synapses. However, in C. elegans, touch neuron-specific knockdown of the E1 ubiquitin-activating enzyme, uba-1, leads to UNC-104 accumulation at neuronal ends and synapses. Here, we performed an RNAi screen and identified that depletion of fbxb-65, which encodes an F-box protein, leads to UNC-104 accumulation at neuronal distal ends, and alters UNC-104 net anterograde movement and levels of UNC-104 on cargo without changing synaptic UNC-104 levels. Split fluorescence reconstitution showed that UNC-104 and FBXB-65 interact throughout the neuron. Our theoretical model suggests that UNC-104 might exhibit cooperative cargo binding that is regulated by FBXB-65. FBXB-65 regulates an unidentified post-translational modification (PTM) of UNC-104 in a region beside the cargo-binding PH domain. Both fbxb-65 and UNC-104, independently of FBXB-65, regulate axonal pre-SV distribution, transport of pre-SVs at branch points and organismal lifespan. FBXB-65 regulates a PTM of UNC-104 and the number of motors on the cargo surface, which can fine-tune cargo transport to the synapse. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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