The interaction of ELKS with Ca2+ channel β subunits may contribute to active zone organization

Abstract

The cytoskeletal matrix of the active zone (CAZ) and synaptic voltage-dependent calcium channels (VDCCs) are both required for the organization and regulation of synaptic vesicle release. Here we report a novel interaction between the CAZ protein family ELKS and VDCC β subunits. We found that two isoforms of ELKS (ELKS2 and ELKS1b) and two isoforms of VDCC β subunits (β1b and β4) co-immunoprecipitated. Using fluorescent immunohistochemistry, we observed colocalization between ELKS1b and VDCC β4 at synapses in the molecular layer of the cerebellum, suggesting a synaptic role for the interaction of these two proteins. Analysis of a P/Q-type VDCC knockout mouse (Cacna1a-/-) revealed that the localization of the VDCC β4 subunit to the molecular layer was disrupted, although ELKS1b protein localization was not affected. The results demonstrate that two isoforms of the ELKS family and two VDCC β subunits interact and suggest that their interaction may play a role in the organization of the active zone