Item

Abstract

Neurotransmitter release is mediated by an evolutionarily conserved machinery. The
synaptic vesicle (SV) associated protein Mover/TPRGL/SVAP30 does not occur in all
species and all synapses. Little is known about its molecular properties and how it may
interact with the conserved components of the presynaptic machinery. Here, we show by
deletion analysis that regions required for homomeric interaction of Mover are distributed
across the entire molecule, including N-terminal, central and C-terminal regions. The
same regions are also required for the accumulation of Mover in presynaptic terminals of
cultured neurons. Mutating two phosphorylation sites in N-terminal regions did not affect
these properties. In contrast, a point mutation in the predicted Calmodulin (CaM) binding
sequence of Mover abolished both homomeric interaction and presynaptic targeting.
We show that this sequence indeed binds Calmodulin, and that recombinant Mover
increases Calmodulin signaling upon heterologous expression. Our data suggest that
presynaptic accumulation of Mover requires homomeric interaction mediated by regions
distributed across large areas of the protein, and corroborate the hypothesis that Mover
functionally interacts with Calmodulin signaling.