Bassoon specifically controls presynaptic P/Q-type Ca(2+) channels via RIM-binding protein.
Voltage-dependent Ca(2+) channels (CaVs) represent the principal source of Ca(2+) ions that trigger evoked neurotransmitter release from presynaptic boutons. Ca(2+) influx is mediated mainly via CaV2.1 (P/Q-type) and CaV2.2 (N-type) channels, which differ in their properties. Their relative contribution to synaptic transmission changes during development and tunes neurotransmission during synaptic plasticity. The mechanism of differential recruitment of CaV2.1 and CaV2.2 to release sites is largely unknown. Here, we show that the presynaptic scaffolding protein Bassoon localizes specifically CaV2.1 to active zones via molecular interaction with the RIM-binding proteins (RBPs). A genetic deletion of Bassoon or an acute interference with Bassoon-RBP interaction reduces synaptic abundance of CaV2.1, weakens P/Q-type Ca(2+) current-driven synaptic transmission, and results in higher relative contribution of neurotransmission dependent on CaV2.2. These data establish Bassoon as a major regulator of the molecular composition of the presynaptic neurotransmitter release sites.
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Daria
D
Davydova
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Claudia
C
Marini
Institute of Neurology, University College London, London WC1N 3BG, UK.
Claire
C
King
Molecular Physiology Group, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Julia
J
Klueva
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Ferdinand
F
Bischof
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Stefano
S
Romorini
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Carolina
C
Montenegro-Venegas
Molecular Physiology Group, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Martin
M
Heine
Molecular Physiology Group, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Romy
R
Schneider
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
Markus S
MS
Schröder
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Center for Behavioral Brain Sciences and Medical Faculty, Otto von Guericke University, 39118 Magdeburg, Germany.
Wilko D
WD
Altrock
Institute of Neurology, University College London, London WC1N 3BG, UK; Institute of Cellular Neuroscience, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
Christian
C
Henneberger
Institute of Neurology, University College London, London WC1N 3BG, UK.
Dmitri A
DA
Rusakov
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Center for Behavioral Brain Sciences and Medical Faculty, Otto von Guericke University, 39118 Magdeburg, Germany. Electronic address: gundelfi@lin-magdeburg.de.
Eckart D
ED
Gundelfinger
Department of Neurochemistry/Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Presynaptic Plasticity Group, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany. Electronic address: afejtova@lin-magdeburg.de.
Anna
A
Fejtova
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D013572:Synaptic Vesicles / Q000187:drug effects; D013997:Time Factors; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D018909:src Homology Domains / Q000502:physiology
D018528:ATP-Binding Cassette Transporters; D002118:Calcium; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D009419:Nerve Tissue Proteins; D020866:omega-Conotoxin GVIA; C512841:Abca4 protein, mouse; C498441:Bsn protein, mouse; C500963:Cacna1b protein, mouse