αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration
Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 [beta 3] integrin in...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2011
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| Online Access: | http://hdl.handle.net/1721.1/60934 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826199863613718528 |
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| author | Gertler, Frank Worth, Daniel C. Hodivala-Dilke, Kairbaan Robinson, Stephen D. King, Samantha J. Morton, Penny E. Humphries, Martin J. Parsons, Maddy |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gertler, Frank Worth, Daniel C. Hodivala-Dilke, Kairbaan Robinson, Stephen D. King, Samantha J. Morton, Penny E. Humphries, Martin J. Parsons, Maddy |
| author_sort | Gertler, Frank |
| collection | MIT |
| description | Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 [beta 3] integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of β3 [beta 3] integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3 [beta 3]-null cells is preferentially associated with Rap1-GTP–interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP–RIAM complex at focal adhesions and subsequent increased binding of talin to β1 [beta 1] integrin. These data demonstrate a novel mechanism by which αvβ3 [alpha nu beta 3]integrin acts to locally suppress β1 [beta 1]integrin activation and regulate protrusion, adhesion dynamics, and persistent migration. |
| first_indexed | 2024-09-23T11:27:01Z |
| format | Article |
| id | mit-1721.1/60934 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:27:01Z |
| publishDate | 2011 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/609342022-10-01T03:41:42Z αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration αvβ3 [alpha nu beta 3] integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration Gertler, Frank Worth, Daniel C. Hodivala-Dilke, Kairbaan Robinson, Stephen D. King, Samantha J. Morton, Penny E. Humphries, Martin J. Parsons, Maddy Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gertler, Frank Gertler, Frank Integrins are fundamental to the control of protrusion and motility in adherent cells. However, the mechanisms by which specific members of this receptor family cooperate in signaling to cytoskeletal and adhesion dynamics are poorly understood. Here, we show that the loss of β3 [beta 3] integrin in fibroblasts results in enhanced focal adhesion turnover and migration speed but impaired directional motility on both 2D and 3D matrices. These motility defects are coupled with an increased rate of actin-based protrusion. Analysis of downstream signaling events reveals that loss of β3 [beta 3] integrin results in a loss of protein kinase A–dependent phosphorylation of the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP). Dephosphorylated VASP in β3 [beta 3]-null cells is preferentially associated with Rap1-GTP–interacting adaptor molecule (RIAM) both in vitro and in vivo, which leads to enhanced formation of a VASP–RIAM complex at focal adhesions and subsequent increased binding of talin to β1 [beta 1] integrin. These data demonstrate a novel mechanism by which αvβ3 [alpha nu beta 3]integrin acts to locally suppress β1 [beta 1]integrin activation and regulate protrusion, adhesion dynamics, and persistent migration. National Institutes of Health (U.S.) (Grant GM50081) 2011-02-11T22:24:35Z 2011-02-11T22:24:35Z 2010-04 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/60934 Worth, D. C. et al. "αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration.” The Journal of Cell Biology 189.2 (2010): 369-383. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1083/jcb.200912014 Journal of Cell Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Rockefeller University Press Rockefeller UP |
| spellingShingle | Gertler, Frank Worth, Daniel C. Hodivala-Dilke, Kairbaan Robinson, Stephen D. King, Samantha J. Morton, Penny E. Humphries, Martin J. Parsons, Maddy αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title | αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title_full | αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title_fullStr | αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title_full_unstemmed | αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title_short | αvβ3 integrin spatially regulates VASP and RIAM to control adhesion dynamics and migration |
| title_sort | αvβ3 integrin spatially regulates vasp and riam to control adhesion dynamics and migration |
| url | http://hdl.handle.net/1721.1/60934 https://orcid.org/0000-0003-3214-4554 |
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