An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling

Ibarra C, Vicencio JM, Varas-Godoy M, Jaimovich E, Rothermel BA, Uhlén P, Hill JA, Lavandero S

Abstract

In cardiomyocytes, Ca2+ plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca2+ within subcellular microdomains: transcription is regulated by Ca2+ release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca2+. Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca2+ signals. However, signaling pathways coupling surface receptor activation to nuclear Ca2+ release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca2+ signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca2+ release from perinudear Ca2+ stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca2+ release. In this review, we discuss mechanisms for the selective control of nuclear Ca2+ signals with special focus on emerging models of agonist receptor activation. (C) 2014 Elsevier Ltd. All rights reserved.

Más información

Título según WOS: An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling
Título según SCOPUS: An integrated mechanism of cardiomyocyte nuclear Ca2+ signaling
Título de la Revista: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volumen: 75
Editorial: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Fecha de publicación: 2014
Página de inicio: 40
Página final: 48
Idioma: English
DOI:

10.1016/j.yjmcc.2014.06.015

Notas: ISI, SCOPUS