We reported recently a new mechanism by which the neuronal N-type Ca(2+) (CaV2.2) channel expression may be regulated by ubiquitination. This mechanism involves the interaction between the channel and the light chain (LC1) of the microtubule associated protein B (MAP1B). We also showed that MAP1B-LC1 could interact with the ubiquitin-conjugating E2 enzyme UBE2L3 and that the ubiquitination/degradation mechanism triggered by MAP1B-LC1 could be prevented by inhibiting the ubiquitin-proteasome proteolytic pathway. We now report that MAP1B-LC1 can interact with the 2 main variants of the CaV2.2 channels (CaV2.2e37a and CaV2.2e37b) and that the MAP1B-LC1-mediated regulation most likely involves an internalization of the channels via a dynamin and clathrin-dependent pathway. In addition, here we propose that this novel mechanism of CaV channel regulation might be conserved among N-type and P/Q-type channels.
Keywords: BFA, brefeldin A; Brefeldin A; DRG, dorsal root ganglion; Dynasore; HVA, high-voltage-activated; LC1; MAP1B; MAP1B-LC1, Microtubule-associated protein 1B light chain; N-type channels; UBE2L3; UBE2L3, Ubiquitin-conjugating enzyme E2 L3; UPS, Ubiquitin proteasome system; trafficking.