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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.
