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

Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5862-7. doi: 10.1073/pnas.1113819109. Epub 2012 Mar 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • FEZ1 protein, human
  • Munc18 Proteins
  • Mutant Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Syntaxin 1
  • UNC-76 protein, C elegans
  • Kinesins