Tetraspanin-13 modulates voltage-gated Ca(V)2.2 Ca(2+) channels

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 Ca(V)2 Ca(2+) channels. We identified tetraspanin-13 (TSPAN-13) as an interaction partner of the α(1) subunit of N-type Ca(V)2.2, but not of P/Q-type Ca(V)2.1 or L- and T-type Ca(2+) channels. Interaction could be located between domain IV of Ca(V)2.2 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 Ca(V)2.2. These data indicate that TSPAN-13 might regulate Ca(V)2.2 Ca(2+) channel activity in defined synaptic membrane compartments and thereby influences transmitter release.