The MAP1B-LC1/UBE2L3 complex catalyzes degradation of cell surface CaV2.2 channels.

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.