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Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter

Item Type:Article
Title:Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter
Creators Name:Chua, J.J.E. and Butkevich, E. and Worseck, J.M. and Kittelmann, M. and Gronborg, M. and Behrmann, E. and Stelzl, U. and Pavlos, N.J. and Lalowski, M.M. and Eimer, S. and Wanker, E.E. and Klopfenstein, D.R. and Jahn, R.
Abstract:Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx. We also show that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phosphorylation, with a conserved site (serine 58) being essential for binding. When expressed in C. elegans, wild-type but not phosphorylation-deficient FEZ1 (S58A) restored axonal transport of Stx. We conclude that FEZ1 operates as a kinesin adaptor for the transport of Stx, with cargo loading and unloading being regulated by protein kinases.
Keywords:Fasciculation and Elongation Protein zeta 1, Transport Defect, Cargo Aggregation, Animals
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:109
Number:15
Page Range:5862-5867
Date:10 April 2012
Official Publication:https://doi.org/10.1073/pnas.1113819109
PubMed:View item in PubMed

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