Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter
| Autor: | Stefan Eimer, Ulrich Stelzl, Reinhard Jahn, Erich E. Wanker, Nathan J. Pavlos, Maciej Lalowski, Josephine M. Worseck, Elmar Behrmann, John Jia En Chua, Dieter R. Klopfenstein, Eugenia Butkevich, Mads Grønborg, Maike Kittelmann |
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| Rok vydání: | 2012 |
| Předmět: |
Munc18 Proteins
Kinesins Syntaxin 1 Nerve Tissue Proteins macromolecular substances Biology Axonal Transport Motor protein 03 medical and health sciences 0302 clinical medicine Animals Humans Phosphorylation Caenorhabditis elegans Caenorhabditis elegans Proteins 030304 developmental biology Adaptor Proteins Signal Transducing 0303 health sciences Multidisciplinary Neuropeptides Signal transducing adaptor protein Biological Sciences Axons Cell biology Transport protein Synaptic vesicle exocytosis Protein Transport HEK293 Cells Mutation Axoplasmic transport Kinesin Mutant Proteins 030217 neurology & neurosurgery Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences; Vol 109 Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences University of Western Australia |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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