A novel region in the CaV2.1 α1 subunit C-terminus regulates fast synaptic vesicle fusion and vesicle docking at the mammalian presynaptic active zone
Matthias Lübbert,
R Oliver Goral,
Rachel Satterfield,
Travis Putzke,
Arn MJM van den Maagdenberg,
Naomi Kamasawa,
Samuel M Young Jr
Affiliations
Matthias Lübbert
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, United States
R Oliver Goral
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, United States; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, United States
Rachel Satterfield
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, United States
Travis Putzke
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, United States
Arn MJM van den Maagdenberg
Departments of Human Genetics and Neurology, Leiden University Medical Center, Leiden, Netherlands
Naomi Kamasawa
Max Planck Florida Electron Microscopy Core, Max Planck Florida Institute for Neuroscience, Jupiter, United States
Research Group Molecular Mechanisms of Synaptic Function, Max Planck Florida Institute for Neuroscience, Jupiter, United States; Department of Anatomy and Cell Biology, University of Iowa, Iowa City, United States; Department of Otolaryngology, University of Iowa, Iowa City, United States; Iowa Neuroscience Institute, University of Iowa, Iowa City, United States; Aging Mind Brain Initiative, University of Iowa, Iowa City, United States
In central nervous system (CNS) synapses, action potential-evoked neurotransmitter release is principally mediated by CaV2.1 calcium channels (CaV2.1) and is highly dependent on the physical distance between CaV2.1 and synaptic vesicles (coupling). Although various active zone proteins are proposed to control coupling and abundance of CaV2.1 through direct interactions with the CaV2.1 α1 subunit C-terminus at the active zone, the role of these interaction partners is controversial. To define the intrinsic motifs that regulate coupling, we expressed mutant CaV2.1 α1 subunits on a CaV2.1 null background at the calyx of Held presynaptic terminal. Our results identified a region that directly controlled fast synaptic vesicle release and vesicle docking at the active zone independent of CaV2.1 abundance. In addition, proposed individual direct interactions with active zone proteins are insufficient for CaV2.1 abundance and coupling. Therefore, our work advances our molecular understanding of CaV2.1 regulation of neurotransmitter release in mammalian CNS synapses.
