The Ca 2+ Channel Subunit Ca V β2a-subunit Down-Regulates Voltage-Activated Ion Current Densities by Disrupting Actin-Dependent Traffic in Chromaffin Cells

Guerra MJ, González-Jamett AM, Báez-Matus X, Navarro-Quezada N, Martínez AD, Neely A, Cárdenas AM

Keywords: ca2+ channels, actin dynamics, protein trafficking, Ca2+ currents


β-Subunits of the Ca2+ channel have been conventionally regarded as auxiliary subunits that regulate the expression and activity of the pore-forming α1 subunit. However, they comprise protein-protein interaction domains, such as a SRC homology 3 domain (SH3) domain, which make them potential signaling molecules. Here we evaluated the role of the β2a subunit of the Ca2+ channels (CaV β2a) and its SH3 domain (β2a-SH3) in late stages of channel trafficking in bovine adrenal chromaffin cells. Cultured bovine adrenal chromaffin cells were injected with CaV β2a or β2a-SH3 under different conditions, in order to acutely interfere with endogenous associations of these proteins. As assayed by whole-cell patch clamp recordings, Ca2+ currents were reduced by CaV β2a in the presence of exogenous α1-interaction domain. β2a-SH3, but not its dimerization-deficient mutant, also reduced Ca2+ currents. Na+ currents were also diminished following β2a-SH3 injection. Furthermore, β2a-SH3 was still able to reduce Ca2+ currents when dynamin-2 function was disrupted, but not when SNARE-dependent exocytosis or actin polymerization was inhibited. Together with the additional finding that both CaV β2a and β2a-SH3 diminished the incorporation of new actin monomers to cortical actin filaments, β2a-SH3 emerges as a signaling module that might down-regulate forward trafficking of ion channels by modulating actin dynamics.

Más información

Volumen: 151
Número: 6
Editorial: American Society for Neurochemistry
Fecha de publicación: 2019
Página de inicio: 703
Página final: 715
Idioma: Inglés
Financiamiento/Sponsor: FONDECYT


Notas: ISI