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

Chua, J. J., Butkevich, E., Worseck, J., Kittelmann, M., Gronborg, M., Behrmann, E., et al. (2012). Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter. Proceedings of the National Academy of Sciences of the United States of America, 109(15), 5862-5867. doi:10.1073/pnas.1113819109.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-E7AA-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-E7AB-9
Genre: Journal Article

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 Creators:
Chua, J. J., Author
Butkevich, E., Author
Worseck, J.1, Author              
Kittelmann, M., Author
Gronborg, M., Author
Behrmann, E., Author
Stelzl, U.2, Author              
Pavlos, N. J., Author
Lalowski, M. M., Author
Eimer, S., Author
Wanker, E. E., Author
Klopfenstein, D. R., Author
Jahn, R., Author
Affiliations:
1Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433554              
2Molecular Interaction Networks (Ulrich Stelzl), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479660              

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Free keywords: Adaptor Proteins, Signal Transducing/*metabolism Animals *Axonal Transport Axons/metabolism Caenorhabditis elegans/metabolism Caenorhabditis elegans Proteins/*metabolism HEK293 Cells Humans Kinesin/*metabolism Munc18 Proteins/metabolism Mutant Proteins/metabolism Mutation/genetics Nerve Tissue Proteins/*metabolism Neuropeptides/*metabolism Phosphorylation Protein Binding Protein Transport Syntaxin 1/*metabolism
 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.

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Language(s): eng - English
 Dates: 2012-03-262012-04-10
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1113819109
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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: National Academy of Sciences
Pages: - Volume / Issue: 109 (15) Sequence Number: - Start / End Page: 5862 - 5867 Identifier: ISSN: 0027-8424
CoNE: /journals/resource/954925427230