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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2019.00249

The Calmodulin Binding Region of the Synaptic Vesicle Protein Mover is Required for Homomeric Interaction and Presynaptic Targeting

 Asha K. Akula1, Xin Zhang2,  Julio S. Viotti1, Rene Ebrecht3, Kerstin Reim4,  Fred Wouters3, Thomas Liepold4,  Olaf Jahn4,  Ivan Bogeski2 and  Thomas Dresbach1*
  • 1Department of Anatomy and Embryology, University of Göttingen, Germany
  • 2Institute of Cardiovascular Physiology, University Medical Center Göttingen, Germany
  • 3Institute of Neuropathology, University Medical Center Göttingen, Germany
  • 4Max Planck Institute for Experimental Medicine, Germany

The synaptic vesicle associated protein Mover / TPRGL / SVAP30 is one of the few vertebrate-specific proteins in the evolutionarily conserved machinery mediating neurotransmitter release. 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 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.

Keywords: Synaptic Vesicles, MOVER, TPRGL, Calmodulin, Presynaptic

Received: 13 Jul 2019; Accepted: 26 Sep 2019.

Copyright: © 2019 Akula, Zhang, Viotti, Ebrecht, Reim, Wouters, Liepold, Jahn, Bogeski and Dresbach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Thomas Dresbach, Department of Anatomy and Embryology, University of Göttingen, Goettingen, Lower Saxony, Germany, thomas.dresbach@med.uni-goettingen.de