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Ca V β controls the endocytic turnover of Ca V 1 .2 L‐type calcium channel
Author(s) -
Conrad Rachel,
Kortzak Daniel,
Guzman Gustavo A.,
MirandaLaferte Erick,
Hidalgo Patricia
Publication year - 2021
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12788
Subject(s) - endocytic cycle , protein subunit , biophysics , depolarization , calcium , biology , intracellular , voltage dependent calcium channel , microbiology and biotechnology , biochemistry , chemistry , cell , endocytosis , organic chemistry , gene
Membrane depolarization activates the multisubunit Ca V 1.2 L‐type calcium channel initiating various excitation coupling responses. Intracellular trafficking into and out of the plasma membrane regulates the channel's surface expression and stability, and thus, the strength of Ca V 1.2‐mediated Ca 2+ signals. The mechanisms regulating the residency time of the channel at the cell membrane are unclear. Here, we coexpressed the channel core complex Ca V 1.2α 1 pore‐forming and auxiliary Ca V β subunits and analyzed their trafficking dynamics from single‐particle‐tracking trajectories. Speed histograms obtained for each subunit were best fitted to a sum of diffusive and directed motion terms. The same mean speed for the highest‐mobility state underlying directed motion was found for all subunits. The frequency of this component increased by covalent linkage of Ca V β to Ca V 1.2α 1 suggesting that high‐speed transport occurs in association with Ca V β. Selective tracking of Ca V 1.2α 1 along the postendocytic pathway failed to show the highly mobile state, implying Ca V β‐independent retrograde transport. Retrograde speeds of Ca V 1.2α 1 are compatible with myosin VI‐mediated backward transport. Moreover, residency time at the cell surface was significantly prolonged when Ca V 1.2α 1 was covalently linked to Ca V β. Thus, Ca V β promotes fast transport speed along anterograde trafficking and acts as a molecular switch controlling the endocytic turnover of L‐type calcium channels.