Autoinhibition of a Neuronal Kinesin UNC-104/KIF1A Regulates the Size and Density of Synapses

Shinsuke Niwa, David M. Lipton, Manatsu Morikawa, Charles Zhao, Nobutaka Hirokawa, Hang Lu, Kang Shen

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Kinesin motor proteins transport intracellular cargoes throughout cells by hydrolyzing ATP and moving along microtubule tracks. Intramolecular autoinhibitory interactions have been shown for several kinesins in vitro; however, the physiological significance of autoinhibition remains poorly understood. Here, we identified four mutations in the stalk region and motor domain of the synaptic vesicle (SV) kinesin UNC-104/KIF1A that specifically disrupt autoinhibition. These mutations augment both microtubule and cargo vesicle binding in vitro. In vivo, these mutations cause excessive activation of UNC-104, leading to decreased synaptic density, smaller synapses, and ectopic localization of SVs in the dendrite. We also show that the SV-bound small GTPase ARL-8 activates UNC-104 by unlocking the autoinhibition. These results demonstrate that the autoinhibitory mechanism is used to regulate the distribution of transport cargoes and is important for synaptogenesis in vivo.

Original languageEnglish
Pages (from-to)2129-2141
Number of pages13
JournalCell Reports
Volume16
Issue number8
DOIs
Publication statusPublished - 2016 Aug 23

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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