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Abstract:
Presynaptic nerve terminals are formed from preassembled vesicles
that are delivered to the prospective synapse by kinesin-mediated
axonal transport. However, precis
ely how the various cargoes are
linked to the motor proteins remains unclear. Here, we report
a transport complex linking syntax
in 1a (Stx) and Munc18, two pro-
teins 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
Caenorhabdi-
tis elegans
causes defects in the axonal transport of Stx. We also show
that binding of FEZ1 to Kinesin-1 and Munc18 is regulated by phos-
phorylation, with a conserved site (s
erine 58) being essential for bind-
ing.Whenexpressedin
C. elegans
,wild-typebutnotphosphorylation-
de
fi
cient 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.
