Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces

Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic ma...

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Main Authors:	Cheng-han Yu, Nisha Bte Mohd Rafiq, Anitha Krishnasamy, Kevin L. Hartman, Gareth E. Jones, Alexander D. Bershadsky, Michael P. Sheetz
Format:	Article
Language:	English
Published:	Elsevier 2013-12-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124713006396

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spelling	doaj-a0299df790664630a4d5626619be626f2020-11-25T01:39:04ZengElsevierCell Reports2211-12472013-12-01551456146810.1016/j.celrep.2013.10.040Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction ForcesCheng-han Yu0Nisha Bte Mohd Rafiq1Anitha Krishnasamy2Kevin L. Hartman3Gareth E. Jones4Alexander D. Bershadsky5Michael P. Sheetz6Mechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeRandall Division of Cell & Molecular Biophysics, King’s College London, London SE1 1UL, UKMechanobiology Institute, National University of Singapore, Singapore 117411, SingaporeMechanobiology Institute, National University of Singapore, Singapore 117411, Singapore Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack matrix metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1–2 μm), these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K) and the production of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) in a FAK/PYK2-dependent manner. Enrichment of PIP3 precedes N-WASP activation and the recruitment of RhoA-GAP ARAP3. We propose that adhesion structures can be modulated by traction force development and that production of PIP3 stimulates podosome formation and subsequent RhoA downregulation in the absence of traction force. http://www.sciencedirect.com/science/article/pii/S2211124713006396
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Cheng-han Yu Nisha Bte Mohd Rafiq Anitha Krishnasamy Kevin L. Hartman Gareth E. Jones Alexander D. Bershadsky Michael P. Sheetz
spellingShingle	Cheng-han Yu Nisha Bte Mohd Rafiq Anitha Krishnasamy Kevin L. Hartman Gareth E. Jones Alexander D. Bershadsky Michael P. Sheetz Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces Cell Reports
author_facet	Cheng-han Yu Nisha Bte Mohd Rafiq Anitha Krishnasamy Kevin L. Hartman Gareth E. Jones Alexander D. Bershadsky Michael P. Sheetz
author_sort	Cheng-han Yu
title	Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces
title_short	Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces
title_full	Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces
title_fullStr	Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces
title_full_unstemmed	Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces
title_sort	integrin-matrix clusters form podosome-like adhesions in the absence of traction forces
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2013-12-01
description	Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD)-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack matrix metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1–2 μm), these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K) and the production of phosphatidylinositol-(3,4,5)-triphosphate (PIP3) in a FAK/PYK2-dependent manner. Enrichment of PIP3 precedes N-WASP activation and the recruitment of RhoA-GAP ARAP3. We propose that adhesion structures can be modulated by traction force development and that production of PIP3 stimulates podosome formation and subsequent RhoA downregulation in the absence of traction force.
url	http://www.sciencedirect.com/science/article/pii/S2211124713006396
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Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces

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