Article

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

Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 03/2012; 109(15):5862-7. DOI: 10.1073/pnas.1113819109
Source: PubMed

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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    • "During neuronal development, Munc18-1/syntaxin-1 and syn- taxin-1 are transported by FEZ1–KIF5C (Chua et al., 2012) and syntabulin–KIF5B (Su et al., 2004; Cai et al., 2007) transport complexes. Our FRAP experiments in axons (Fig. 3) showed identical recovery of Munc18-1-Venus and Stx-YFP and increased Munc18-1-Venus recovery after cleavage of syntaxin-1, which indicates that lateral diffusion via membrane-bound syn- taxin-1 rather than active transport of organelles is the main mode of delivering Munc18-1 to release sites in mature neurons . "
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