title: Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels.
abstract: Integration of voltage-gated Ca(2+) channels in a network of protein-interactions is a crucial requirement for proper regulation of channel activity. In this study, we took advantage of the specific properties of the yeast split-ubiquitin system to search for and characterize so far unknown interaction partners of CaV2 Ca(2+) channels. We identified tetraspanin-13 (TSPAN-13) as an interaction partner of the α1 subunit of N-type CaV2.2, but not of P/Q-type CaV2.1 or L- and T-type Ca(2+) channels. Interaction could be located between domain IV of CaV2.2 and transmembrane segments S1 and S2 of TSPAN-13. Electrophysiological analysis revealed that TSPAN-13 specifically modulates the efficiency of coupling between voltage sensor activation and pore opening of the channel and accelerates the voltage-dependent activation and inactivation of the Ba(2+) current through CaV2.2. These data indicate that TSPAN-13 might regulate CaV2.2 Ca(2+) channel activity in defined synaptic membrane compartments and thereby influences transmitter release.
authors: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
authors: Robert T
authors: RT
authors: Mallmann
authors: Thomas
authors: T
authors: Wilmes
authors: Lucia
authors: L
authors: Lichvarova
authors: Anja
authors: A
authors: Bührer
authors: Barbara
authors: B
authors: Lohmüller
authors: Jan
authors: J
authors: Castonguay
authors: Lubica
authors: L
authors: Lacinova
authors: Norbert
authors: N
authors: Klugbauer
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D021122:Protein Subunits / Q000378:metabolism; D059470:Tetraspanins / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism
chemical_list: D001464:Barium; D002118:Calcium; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D059470:Tetraspanins; D025801:Ubiquitin
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