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...
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2021.769321/full |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T03:38:53Z |
| format | Article |
| id | doaj.art-b6c861a501b04149a3eadb02596c81fa |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-19T03:38:53Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Physiology |
| spelling | doaj.art-b6c861a501b04149a3eadb02596c81fa2022-12-21T20:37:18ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2021-11-011210.3389/fphys.2021.769321769321Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle CellsAlexandra Sporkova0Subhajit Ghosh1Jaafar Al-Hasani2Jaafar Al-Hasani3Markus Hecker4Markus Hecker5Department of Cardiovascular Physiology, Heidelberg University, Heidelberg, GermanyDepartment of Cardiovascular Physiology, Heidelberg University, Heidelberg, GermanyDepartment of Cardiovascular Physiology, Heidelberg University, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research) Partner Site, Heidelberg/Mannheim, GermanyDepartment of Cardiovascular Physiology, Heidelberg University, Heidelberg, GermanyDZHK (German Centre for Cardiovascular Research) Partner Site, Heidelberg/Mannheim, GermanyArterial 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.https://www.frontiersin.org/articles/10.3389/fphys.2021.769321/fulllipoma preferred partnerzyxinmechanosensingmechanotransductionLIM domain proteinsvascular cells |
| spellingShingle | 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 Frontiers in Physiology lipoma preferred partner zyxin mechanosensing mechanotransduction LIM domain proteins vascular cells |
| title | 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_short | 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 |
| topic | lipoma preferred partner zyxin mechanosensing mechanotransduction LIM domain proteins vascular cells |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2021.769321/full |
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