María J. GuerraXimena Báez‐MatusNieves Navarro‐QuezadaCárdenas, AnaAnaCárdenasGonzález, ArlekArlekGonzálezMartínez, AgustínAgustínMartínezNeely, AlanAlanNeely2025-04-152025-04-152019-08-1610.1111/jnc.148512-s2.0-85076532096https://cris-uv-2.scimago.es/handle/123456789/2381WOS:000494093700001Abstract β‐Subunits of the Ca 2+ channel have been conventionally regarded as auxiliary subunits that regulate the expression and activity of the pore‐forming α 1 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 Ca 2+ channels (Ca V 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 Ca V 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, Ca 2+ currents were reduced by Ca V β2a in the presence of exogenous α1‐interaction domain. β2a‐SH3, but not its dimerization‐deficient mutant, also reduced Ca 2+ currents. Na + currents were also diminished following β2a‐SH3 injection. Furthermore, β2a‐SH3 was still able to reduce Ca 2+ 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 Ca V 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. imageenacceso abiertoBiochemistry And Molecular BiologyBiochemistryCellular And Molecular NeuroscienceNeurosciencesarticle