Putative mechanism through which N-cadherin-mediated cell contact maintains calcium homeostasis and thereby prevents ovarian cells from undergoing apoptosis.
To date most of the studies involving the maintenance of ovarian cell viability have focused on the endocrine, paracrine, and autocrine factors that inhibit these cells from undergoing programmed cell death or apoptosis. Recently, studies have demonstrated that cell contact also prevents ovarian cells from dying via an apoptotic mechanism. In this commentary, the role that homophilic binding of the cell adhesion molecule, N-cadherin, plays in maintaining ovarian cell viability is presented. These studies showed that N-cadherin homophilic binding (1) is part of the mechanism through which cell contact maintains cell viability, (2) results in the activation (i.e. tyrosine phosphorylation) of the fibroblast growth factor (FGF) receptor, and (3) prevents a sustained elevation in intracellular free calcium ([Ca2+]i) which triggers apoptosis. These studies also revealed that hepatocyte growth factor (HGF), also known as scatter factor (SF), disrupts cell contact, which leads to a sustained increase in [Ca2+]i levels and ultimately to cell death. Based on these studies, this commentary presents a putative mechanism that relates the cellular and molecular mechanism through which basic FGF, N-cadherin, and HGF/SF interact to regulate [Ca2+]i levels and ultimately ovarian cell survival.
Peluso
J J
JJ
Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington 06030, U.S.A.
D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication; D002470:Cell Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D006107:Granulosa Cells / Q000166:cytology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D010053:Ovary / Q000166:cytology*; D015398:Signal Transduction
D015820:Cadherins; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D002118:Calcium