α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways

Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function a...

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Autores principales:	Willow Hight-Warburton, Robert Felix, Andrew Burton, Hannah Maple, Magda S. Chegkazi, Roberto A. Steiner, John A. McGrath, Maddy Parsons
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	integrin alpha4 integrin alpha9 MAP kinase cell movement actin cytoskeleton Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/611a606d3f5e4468ae98a523635ec3f2
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spelling	oai:doaj.org-article:611a606d3f5e4468ae98a523635ec3f22021-12-01T01:15:11Zα4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways2296-634X10.3389/fcell.2021.750771https://doaj.org/article/611a606d3f5e4468ae98a523635ec3f22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.750771/fullhttps://doaj.org/toc/2296-634XAdhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4β1 and α9β1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4β1 and α9β1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4β1 and α9β1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting CCM. Further analysis revealed that α4β1/α9β1 integrins suppress extracellular signal-regulated kinase (ERK1/2) activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). This work demonstrates the roles of α4β1 and α9β1 in regulating migration in response to damage cues.Willow Hight-WarburtonRobert FelixAndrew BurtonHannah MapleMagda S. ChegkaziRoberto A. SteinerRoberto A. SteinerJohn A. McGrathMaddy ParsonsFrontiers Media S.A.articleintegrin alpha4integrin alpha9MAP kinasecell movementactin cytoskeletonBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	integrin alpha4 integrin alpha9 MAP kinase cell movement actin cytoskeleton Biology (General) QH301-705.5
spellingShingle	integrin alpha4 integrin alpha9 MAP kinase cell movement actin cytoskeleton Biology (General) QH301-705.5 Willow Hight-Warburton Robert Felix Andrew Burton Hannah Maple Magda S. Chegkazi Roberto A. Steiner Roberto A. Steiner John A. McGrath Maddy Parsons α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
description	Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4β1 and α9β1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4β1 and α9β1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4β1 and α9β1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting CCM. Further analysis revealed that α4β1/α9β1 integrins suppress extracellular signal-regulated kinase (ERK1/2) activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). This work demonstrates the roles of α4β1 and α9β1 in regulating migration in response to damage cues.
format	article
author	Willow Hight-Warburton Robert Felix Andrew Burton Hannah Maple Magda S. Chegkazi Roberto A. Steiner Roberto A. Steiner John A. McGrath Maddy Parsons
author_facet	Willow Hight-Warburton Robert Felix Andrew Burton Hannah Maple Magda S. Chegkazi Roberto A. Steiner Roberto A. Steiner John A. McGrath Maddy Parsons
author_sort	Willow Hight-Warburton
title	α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
title_short	α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
title_full	α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
title_fullStr	α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
title_full_unstemmed	α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways
title_sort	α4/α9 integrins coordinate epithelial cell migration through local suppression of map kinase signaling pathways
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/611a606d3f5e4468ae98a523635ec3f2
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α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways

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