AUTHOR=Akula Asha Kiran , Zhang Xin , Viotti Julio S. , Nestvogel Dennis , Rhee Jeong-Seop , Ebrecht Rene , Reim Kerstin , Wouters Fred , Liepold Thomas , Jahn Olaf , Bogeski Ivan , Dresbach Thomas TITLE=The Calmodulin Binding Region of the Synaptic Vesicle Protein Mover Is Required for Homomeric Interaction and Presynaptic Targeting JOURNAL=Frontiers in Molecular Neuroscience VOLUME=12 YEAR=2019 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2019.00249 DOI=10.3389/fnmol.2019.00249 ISSN=1662-5099 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.