Journal Article

FZJ-2021-02069

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Ca V β controls the endocytic turnover of Ca V 1 .2 L‐type calcium channel

Conrad, R.FZJ* ; Kortzak, D.FZJ* ; Guzman, G. A.FZJ* ; Miranda-Laferte, E.FZJ* ; Hidalgo, P. (Corresponding author)FZJ*

2021
Wiley-Blackwell Oxford

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Please use a persistent id in citations: http://hdl.handle.net/2128/27890  doi:10.1111/tra.12788

Abstract: Membrane depolarization activates the multisubunit CaV1.2 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 CaV1.2-mediated Ca2+ signals. The mechanisms regulating the residency time of the channel at the cell membrane are unclear. Here, we coexpressed the channel core complex CaV1.2α1 pore-forming and auxiliary CaVβ 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 CaVβ to CaV1.2α1 suggesting that high-speed transport occurs in association with CaVβ. Selective tracking of CaV1.2α1 along the postendocytic pathway failed to show the highly mobile state, implying CaVβ-independent retrograde transport. Retrograde speeds of CaV1.2α1 are compatible with myosin VI-mediated backward transport. Moreover, residency time at the cell surface was significantly prolonged when CaV1.2α1 was covalently linked to CaVβ. Thus, CaVβ promotes fast transport speed along anterograde trafficking and acts as a molecular switch controlling the endocytic turnover of L-type calcium channels.

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Contributing Institute(s):

1. Molekular- und Zellphysiologie (IBI-1)

Research Program(s):

1. 524 - Molecular and Cellular Information Processing (POF4-524) (POF4-524)

Appears in the scientific report 2021

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Database coverage:
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