Stac proteins associate with the critical domain for excitation-contraction coupling in the II-III loop of CaV 1.1

The Journal of General Physiology
Alexander PolsterKurt G Beam

Abstract

In skeletal muscle, residues 720-764/5 within the CaV1.1 II-III loop form a critical domain that plays an essential role in transmitting the excitation-contraction (EC) coupling Ca2+ release signal to the type 1 ryanodine receptor (RyR1) in the sarcoplasmic reticulum. However, the identities of proteins that interact with the loop and its critical domain and the mechanism by which the II-III loop regulates RyR1 gating remain unknown. Recent work has shown that EC coupling in skeletal muscle of fish and mice depends on the presence of Stac3, an adaptor protein that is highly expressed only in skeletal muscle. Here, by using colocalization as an indicator of molecular interactions, we show that Stac3, as well as Stac1 and Stac2 (predominantly neuronal Stac isoforms), interact with the II-III loop of CaV1.1. Further, we find that these Stac proteins promote the functional expression of CaV1.1 in tsA201 cells and support EC coupling in Stac3-null myotubes and that Stac3 is the most effective. Coexpression in tsA201 cells reveals that Stac3 interacts only with II-III loop constructs containing the majority of the CaV1.1 critical domain residues. By coexpressing Stac3 in dysgenic (CaV1.1-null) myotubes together with CaV1 constructs w...Continue Reading

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Citations

Aug 3, 2018·Journal of Cellular Physiology·Marta CampiglioBernhard E Flucher
Jun 23, 2019·Journal of Neuromuscular Diseases·Uluç YişYavuz Oktay
Feb 8, 2019·The Journal of General Physiology·Eduardo RíosClara Franzini-Armstrong
Jun 29, 2018·The Journal of General Physiology·Jacqueline NiuManu Ben-Johny
Feb 6, 2020·The Journal of General Physiology·Robert C KlippJohn R Bankston
Jul 22, 2018·Skeletal Muscle·Erick O Hernández-Ochoa, Martin F Schneider
May 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Bernd R GardillFilip Van Petegem
Mar 31, 2020·Pflügers Archiv : European journal of physiology·Bernhard E Flucher
Dec 17, 2020·Journal of Neuromuscular Diseases·Jean-François DesaphyBertrand Fontaine
Jul 20, 2021·Physiological Reviews·Kellie A Woll, Filip Van Petegem
Sep 13, 2018·Annual Review of Genetics·Raika Pancaroglu, Filip Van Petegem

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Datasets Mentioned

BETA
X05921
.1
X15539

Methods Mentioned

BETA
PCR
fluorescence after photobleaching
transfections

Software Mentioned

Clampex
SigmaPlot
ZEN

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