Tetraspanin-13 Modulates Voltage-Gated CaV2.2 Ca2+ Channels

Sci Rep. 2013;3:1777. doi: 10.1038/srep01777.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Barium / metabolism
  • CHO Cells
  • Calcium / metabolism*
  • Calcium Channels, L-Type / metabolism*
  • Calcium Channels, N-Type / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • HEK293 Cells
  • Humans
  • Protein Subunits / metabolism
  • Tetraspanins / metabolism*
  • Ubiquitin / metabolism
  • Yeasts / metabolism

Substances

  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Protein Subunits
  • Tetraspanins
  • Ubiquitin
  • voltage-dependent calcium channel (P-Q type)
  • Barium
  • Calcium