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Biochim Biophys Acta Mol Cell Res. 2019 Aug;1866(8):1249-1259. doi: 10.1016/j.bbamcr.2019.03.017. Epub 2019 Apr 2.

MURC/CAVIN-4 facilitates store-operated calcium entry in neonatal cardiomyocytes.

Author information

1
Département de Pharmacologie et Physiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, QC J1H 5N4, Canada; Département de Médecine - Service de Cardiologie, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
2
Département de Médecine - Service de Rhumatologie, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
3
Département de Médecine - Service de Cardiologie, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
4
Département de Pharmacologie et Physiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, QC J1H 5N4, Canada.
5
Département de Médecine - Service de Rhumatologie, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Institut de Pharmacologie de Sherbrooke, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
6
Département de Médecine - Service de Cardiologie, Centre de Recherche du CHUS, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Institut de Pharmacologie de Sherbrooke, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. Electronic address: Mannix.Auger-Messier@USherbrooke.ca.
7
Département de Pharmacologie et Physiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, QC J1H 5N4, Canada; Institut de Pharmacologie de Sherbrooke, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada. Electronic address: Guylain.Boulay@USherbrooke.ca.

Abstract

Intact store-operated calcium entry (SOCE) mechanisms ensure the maintenance of Ca2+ homeostasis in cardiomyocytes while their dysregulation promotes the development of cardiomyopathies. To better understand this calcium handling process in cardiomyocytes, we sought to identify unknown protein partners of stromal interaction molecule 1 (STIM1), a main regulatory protein of SOCE. We identified the muscle-related coiled-coil protein (MURC), also known as Cavin-4, as a candidate and showed that MURC interacts with STIM1 in cardiomyocytes. This interaction occurs via the HR1 and ERM domains of MURC and STIM1, respectively. Our results also demonstrated that the overexpression of MURC in neonatal rat ventricular myocytes (NRVM) is sufficient to potentiate SOCE and that its HR1 domain is required to mediate this effect. Interestingly, the R140W-MURC mutant, a missense variant of the HR1 domain associated with human dilated cardiomyopathy, exacerbates the SOCE increase in NRVM. Although the endogenous expression of STIM1 and Ca2+ channel Orai1 is not modulated under these conditions, we showed that MURC increases the interaction between these proteins under resting conditions. Our study provides novel evidence that MURC regulates SOCE by interacting with STIM1 in cardiomyocytes. In addition, we identified a first potential mechanism by which the R140W mutation of MURC may contribute to calcium mishandling and the development of cardiomyopathies.

KEYWORDS:

Cardiomyocyte; Cavin-4; MURC; Orai1; STIM1; Store-operated calcium entry

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