The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.

Motile cells are capable of sensing the stiffness of the surrounding extracellular matrix through integrin-mediated focal adhesions and migrate towards regions of higher rigidity in a process known as durotaxis. Durotaxis plays an important role in normal development and disease progression, includi...

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Autores principales:	Duncan B Wormer, Kevin A Davis, James H Henderson, Christopher E Turner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f62dc6c97b60473e96a1d0496e88fca0
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spelling	oai:doaj.org-article:f62dc6c97b60473e96a1d0496e88fca02021-11-18T08:28:02ZThe focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.1932-620310.1371/journal.pone.0091815https://doaj.org/article/f62dc6c97b60473e96a1d0496e88fca02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24632816/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Motile cells are capable of sensing the stiffness of the surrounding extracellular matrix through integrin-mediated focal adhesions and migrate towards regions of higher rigidity in a process known as durotaxis. Durotaxis plays an important role in normal development and disease progression, including tumor invasion and metastasis. However, the signaling mechanisms underlying focal adhesion-mediated rigidity sensing and durotaxis are poorly understood. Utilizing matrix-coated polydimethylsiloxane gels to manipulate substrate compliance, we show that cdGAP, an adhesion-localized Rac1 and Cdc42 specific GTPase activating protein, is necessary for U2OS osteosarcoma cells to coordinate cell shape changes and migration as a function of extracellular matrix stiffness. CdGAP regulated rigidity-dependent motility by controlling membrane protrusion and adhesion dynamics, as well as by modulating Rac1 activity. CdGAP was also found to be necessary for U2OS cell durotaxis. Taken together, these data identify cdGAP as an important component of an integrin-mediated signaling pathway that senses and responds to mechanical cues in the extracellular matrix in order to coordinate directed cell motility.Duncan B WormerKevin A DavisJames H HendersonChristopher E TurnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e91815 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Duncan B Wormer Kevin A Davis James H Henderson Christopher E Turner The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
description	Motile cells are capable of sensing the stiffness of the surrounding extracellular matrix through integrin-mediated focal adhesions and migrate towards regions of higher rigidity in a process known as durotaxis. Durotaxis plays an important role in normal development and disease progression, including tumor invasion and metastasis. However, the signaling mechanisms underlying focal adhesion-mediated rigidity sensing and durotaxis are poorly understood. Utilizing matrix-coated polydimethylsiloxane gels to manipulate substrate compliance, we show that cdGAP, an adhesion-localized Rac1 and Cdc42 specific GTPase activating protein, is necessary for U2OS osteosarcoma cells to coordinate cell shape changes and migration as a function of extracellular matrix stiffness. CdGAP regulated rigidity-dependent motility by controlling membrane protrusion and adhesion dynamics, as well as by modulating Rac1 activity. CdGAP was also found to be necessary for U2OS cell durotaxis. Taken together, these data identify cdGAP as an important component of an integrin-mediated signaling pathway that senses and responds to mechanical cues in the extracellular matrix in order to coordinate directed cell motility.
format	article
author	Duncan B Wormer Kevin A Davis James H Henderson Christopher E Turner
author_facet	Duncan B Wormer Kevin A Davis James H Henderson Christopher E Turner
author_sort	Duncan B Wormer
title	The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
title_short	The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
title_full	The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
title_fullStr	The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
title_full_unstemmed	The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.
title_sort	focal adhesion-localized cdgap regulates matrix rigidity sensing and durotaxis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f62dc6c97b60473e96a1d0496e88fca0
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The focal adhesion-localized CdGAP regulates matrix rigidity sensing and durotaxis.

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