Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells

Arterial hypertension is the leading risk factor for cardiovascular morbidity and mortality worldwide. However, little is known about the cellular mechanisms underlying it. In small arteries and arterioles, a chronic increase in blood pressure raises wall tension and hence stretches, namely, the med...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alexandra Sporkova, Subhajit Ghosh, Jaafar Al-Hasani, Markus Hecker
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	lipoma preferred partner zyxin mechanosensing mechanotransduction LIM domain proteins vascular cells Physiology QP1-981
Acceso en línea:	https://doaj.org/article/b6c861a501b04149a3eadb02596c81fa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b6c861a501b04149a3eadb02596c81fa
record_format	dspace
spelling	oai:doaj.org-article:b6c861a501b04149a3eadb02596c81fa2021-11-19T07:48:41ZLin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells1664-042X10.3389/fphys.2021.769321https://doaj.org/article/b6c861a501b04149a3eadb02596c81fa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.769321/fullhttps://doaj.org/toc/1664-042XArterial hypertension is the leading risk factor for cardiovascular morbidity and mortality worldwide. However, little is known about the cellular mechanisms underlying it. In small arteries and arterioles, a chronic increase in blood pressure raises wall tension and hence stretches, namely, the medial vascular smooth muscle cells (VSMC) but also endothelial cell (EC) to cell contacts. Initially compensated by an increase in vascular tone, the continuous biomechanical strain causes a prominent change in gene expression in both cell types, frequently driving an arterial inward remodeling process that ultimately results in a reduction in lumen diameter, stiffening of the vessel wall, and fixation of blood pressure, namely, diastolic blood pressure, at the elevated level. Sensing and propagation of this supraphysiological stretch into the nucleus of VSMC and EC therefore seems to be a crucial step in the initiation and advancement of hypertension-induced arterial remodeling. Focal adhesions (FA) represent an important interface between the extracellular matrix and Lin11-Isl1-Mec3 (LIM) domain-containing proteins, which can translocate from the FA into the nucleus where they affect gene expression. The varying biomechanical cues to which vascular cells are exposed can thus be rapidly and specifically propagated to the nucleus. Zyxin was the first protein described with such mechanotransducing properties. It comprises 3 C-terminal LIM domains, a leucine-rich nuclear export signal, and N-terminal features that support its association with the actin cytoskeleton. In the cytoplasm, zyxin promotes actin assembly and organization as well as cell motility. In EC, zyxin acts as a transcription factor, whereas in VSMC, it has a less direct effect on mechanosensitive gene expression. In terms of homology and structural features, lipoma preferred partner is the nearest relative of zyxin among the LIM domain proteins. It is almost exclusively expressed by smooth muscle cells in the adult, resides like zyxin at FA but seems to affect mechanosensitive gene expression indirectly, possibly via altering cortical actin dynamics. Here, we highlight what is currently known about the role of these LIM domain proteins in mechanosensing and transduction in vascular cells.Alexandra SporkovaSubhajit GhoshJaafar Al-HasaniJaafar Al-HasaniMarkus HeckerMarkus HeckerFrontiers Media S.A.articlelipoma preferred partnerzyxinmechanosensingmechanotransductionLIM domain proteinsvascular cellsPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lipoma preferred partner zyxin mechanosensing mechanotransduction LIM domain proteins vascular cells Physiology QP1-981
spellingShingle	lipoma preferred partner zyxin mechanosensing mechanotransduction LIM domain proteins vascular cells Physiology QP1-981 Alexandra Sporkova Subhajit Ghosh Jaafar Al-Hasani Jaafar Al-Hasani Markus Hecker Markus Hecker Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
description	Arterial hypertension is the leading risk factor for cardiovascular morbidity and mortality worldwide. However, little is known about the cellular mechanisms underlying it. In small arteries and arterioles, a chronic increase in blood pressure raises wall tension and hence stretches, namely, the medial vascular smooth muscle cells (VSMC) but also endothelial cell (EC) to cell contacts. Initially compensated by an increase in vascular tone, the continuous biomechanical strain causes a prominent change in gene expression in both cell types, frequently driving an arterial inward remodeling process that ultimately results in a reduction in lumen diameter, stiffening of the vessel wall, and fixation of blood pressure, namely, diastolic blood pressure, at the elevated level. Sensing and propagation of this supraphysiological stretch into the nucleus of VSMC and EC therefore seems to be a crucial step in the initiation and advancement of hypertension-induced arterial remodeling. Focal adhesions (FA) represent an important interface between the extracellular matrix and Lin11-Isl1-Mec3 (LIM) domain-containing proteins, which can translocate from the FA into the nucleus where they affect gene expression. The varying biomechanical cues to which vascular cells are exposed can thus be rapidly and specifically propagated to the nucleus. Zyxin was the first protein described with such mechanotransducing properties. It comprises 3 C-terminal LIM domains, a leucine-rich nuclear export signal, and N-terminal features that support its association with the actin cytoskeleton. In the cytoplasm, zyxin promotes actin assembly and organization as well as cell motility. In EC, zyxin acts as a transcription factor, whereas in VSMC, it has a less direct effect on mechanosensitive gene expression. In terms of homology and structural features, lipoma preferred partner is the nearest relative of zyxin among the LIM domain proteins. It is almost exclusively expressed by smooth muscle cells in the adult, resides like zyxin at FA but seems to affect mechanosensitive gene expression indirectly, possibly via altering cortical actin dynamics. Here, we highlight what is currently known about the role of these LIM domain proteins in mechanosensing and transduction in vascular cells.
format	article
author	Alexandra Sporkova Subhajit Ghosh Jaafar Al-Hasani Jaafar Al-Hasani Markus Hecker Markus Hecker
author_facet	Alexandra Sporkova Subhajit Ghosh Jaafar Al-Hasani Jaafar Al-Hasani Markus Hecker Markus Hecker
author_sort	Alexandra Sporkova
title	Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
title_short	Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
title_full	Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
title_fullStr	Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
title_full_unstemmed	Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells
title_sort	lin11-isl1-mec3 domain proteins as mechanotransducers in endothelial and vascular smooth muscle cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/b6c861a501b04149a3eadb02596c81fa
work_keys_str_mv	AT alexandrasporkova lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells AT subhajitghosh lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells AT jaafaralhasani lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells AT jaafaralhasani lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells AT markushecker lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells AT markushecker lin11isl1mec3domainproteinsasmechanotransducersinendothelialandvascularsmoothmusclecells
_version_	1718420281034276864

Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells

Ejemplares similares