title: The MAP1B-LC1/UBE2L3 complex catalyzes degradation of cell surface CaV2.2 channels.
abstract: 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.
authors.affiliation: a Department of Cell Biology; Center for Research and Advanced Studies of the National Polytechnic Institute ; Mexico City , Mexico.
authors.forename: María A
authors.initials: MA
authors.lastname: Gandini
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sandoval
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Zamponi
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
mesh_terms: D055162:Biocatalysis; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
chemical_list: D020864:Calcium Channels, N-Type; C475491:MAP1B protein, human; D008869:Microtubule-Associated Proteins; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes
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