Direct interaction and functional coupling between voltage-gated CaV1.3 Ca2+ channel and GABAB receptor subunit 2

Although CaV1.2 and CaV1.3 are two subtypes of L-type Ca2+ channels expressed in the CNS, functions of CaV1.3 have not been well elucidated compared to CaV1.2. Here, we found that CaV1.3-NT associates with GABABR2-CT using yeast two-hybrid, GST pull-down and co-immunoprecipitation assays. We also demonstrated co-localization of CaV1.3 and GABABR2 in HEK293 cells and cultured hippocampal neurons. Whole-cell patch-clamp and Ca2+-imaging experiments revealed that activation of GABABR increases CaV1.3 currents and intracellular Ca2+ via CaV1.3, but not CaV1.2. These results show a physical and functional interaction between CaV1.3 and GABABR, suggesting the potential pivotal roles of CaV1.3 in the CNS.Structured summaryMINT-7975667: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by two hybrid (MI:0018)MINT-7975740: Cav1.3 (uniprotkb:P27732) and GABABR2 (uniprotkb:O75899) colocalize (MI:0403) by fluorescence microscopy (MI:0416)MINT-7966007, MINT-7966016: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by anti bait coimmunoprecipitation (MI:0006)MINT-7975712, MINT-7975691: Cav1.3 (uniprotkb:P27732) physically interacts (MI:0915) with GABABR2 (uniprotkb:O88871) by pull down (MI:0096)MINT-7966026: GABABR2 (uniprotkb:O88871) and Cav1.3 (uniprotkb:P27732) colocalize (MI:0403) by fluorescence microscopy (MI:0416)