title: Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter.
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.
authors.affiliation: Department of Neurobiology,  Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen,  Germany.
authors.forename: John Jia En
authors.initials: JJ
authors.lastname: Chua
authors.forename: Eugenia
authors.initials: E
authors.lastname: Butkevich
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Worseck
authors.forename: Maike
authors.initials: M
authors.lastname: Kittelmann
authors.forename: Mads
authors.initials: M
authors.lastname: Grønborg
authors.forename: Elmar
authors.initials: E
authors.lastname: Behrmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stelzl
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Pavlos
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Lalowski
authors.forename: Stefan
authors.initials: S
authors.lastname: Eimer
authors.forename: Erich E
authors.initials: EE
authors.lastname: Wanker
authors.forename: Dieter Robert
authors.initials: DR
authors.lastname: Klopfenstein
authors.forename: Reinhard
authors.initials: R
authors.lastname: Jahn
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051938:Munc18 Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D050827:Syntaxin 1 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; C528597:FEZ1 protein, human; D051938:Munc18 Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050827:Syntaxin 1; C105447:UNC-76 protein, C elegans; D016547:Kinesins