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Comments on Chua JJ et al. (2012) Proc Natl Acad Sci U S A "Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter." (0)
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Chua JJ, Butkevich E, Worseck JM, Kittelmann M, Gronborg M, Behrmann E, Stelzl U, Pavlos NJ, Lalowski MM, Eimer S, Wanker EE, Klopfenstein DR, & Jahn R (2012). Phosphorylation-regulated axonal dependent transport of syntaxin 1 is mediated by a Kinesin-1 adapter. Proc Natl Acad Sci U S A, 109, 5862-7. doi:10.1073/pnas.1113819109
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: Chua JJ, Butkevich E, Worseck JM, Kittelmann M, Gronborg M, Behrmann E, Stelzl U, Pavlos NJ, Lalowski MM, Eimer S, Wanker EE, Klopfenstein DR, Jahn R