title: Estrogen receptor alpha interacts with Galpha13 to drive actin remodeling and endothelial cell migration via the RhoA/Rho kinase/moesin pathway.
abstract: Sex steroids control cell movement and tissue organization; however, little is known of the involved mechanisms. This report describes the ongoing dynamic regulation by estrogen of the actin cytoskeleton and cell movement in human vascular endothelial cells that depends on rapid activation of the actin-regulatory protein moesin. Moesin activation is triggered by the interaction of the C-terminal portion of cell membrane estrogen receptor alpha with the G protein Galpha(13), leading to activation of the small GTPase RhoA and of the downstream effector Rho-associated kinase. The resulting phosphorylation of moesin on Thr(558) is the means of moesin's binding to actin and the remodeling of the actin cytoskeleton. This cascade of events ensues within minutes of estradiol administration and results in changes in cell morphology and to the development of specialized cell membrane structures such as ruffles and pseudopodia that are necessary for cell movement. These findings expand our knowledge of the basis of estrogen's effects on human cells, including the regulation of actin assembly, cell movement and migration. They highlight novel pathways of signal transduction of estrogen receptor alpha through nontranscriptional mechanisms. Furthermore, exposure of this estrogen receptor-dependent, nongenomic action of estrogen on human vascular endothelial cells is especially relevant to the present interest in the role of estrogen in cardiovascular protection.
authors.affiliation: Molecular and Cellular Gynecological Endocrinology Laboratory, Department of Reproductive Medicine and Child Development, University of Pisa, Italy. t.simoncini@obgyn.med.unipi.it
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.forename: Camila
authors.initials: C
authors.lastname: Scorticati
authors.forename: Paolo
authors.initials: P
authors.lastname: Mannella
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fadiel
authors.forename: Maria S
authors.initials: MS
authors.lastname: Giretti
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Chiara
authors.initials: C
authors.lastname: Baldacci
authors.forename: Silvia
authors.initials: S
authors.lastname: Garibaldi
authors.forename: Antonella
authors.initials: A
authors.lastname: Caruso
authors.forename: Letizia
authors.initials: L
authors.lastname: Fornari
authors.forename: Frederick
authors.initials: F
authors.lastname: Naftolin
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: D000199:Actins / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D042783:Endothelial Cells / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism* / Q000502:physiology; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D020257:Ventricular Remodeling / Q000502:physiology; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: D000199:Actins; D047628:Estrogen Receptor alpha; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; C071058:moesin; D004958:Estradiol; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020742:rhoA GTP-Binding Protein