Mena binds α5 integrin directly and modulates α5β1 function
Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β...
| Main Authors: | , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Rockefeller University Press, The
2012
|
| Online Access: | http://hdl.handle.net/1721.1/74675 https://orcid.org/0000-0003-3214-4554 https://orcid.org/0000-0002-3048-7927 https://orcid.org/0000-0001-7603-8396 |
| _version_ | 1826216990152327168 |
|---|---|
| author | Gupton, Stephanie L. Riquelme, Daisy Noelia Hughes-Alford, Shannon Kay Tadros, Jenny Rudina, Shireen S. Hynes, Richard O. Lauffenburger, Douglas A. Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Gupton, Stephanie L. Riquelme, Daisy Noelia Hughes-Alford, Shannon Kay Tadros, Jenny Rudina, Shireen S. Hynes, Richard O. Lauffenburger, Douglas A. Gertler, Frank |
| author_sort | Gupton, Stephanie L. |
| collection | MIT |
| description | Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue “LERER” repeats. In fibroblasts, the Mena–α5 complex was required for “outside-in” α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins. |
| first_indexed | 2024-09-23T16:56:39Z |
| format | Article |
| id | mit-1721.1/74675 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:56:39Z |
| publishDate | 2012 |
| publisher | Rockefeller University Press, The |
| record_format | dspace |
| spelling | mit-1721.1/746752022-09-29T22:32:47Z Mena binds α5 integrin directly and modulates α5β1 function Gupton, Stephanie L. Riquelme, Daisy Noelia Hughes-Alford, Shannon Kay Tadros, Jenny Rudina, Shireen S. Hynes, Richard O. Lauffenburger, Douglas A. Gertler, Frank Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gupton, Stephanie L. Riquelme, Daisy Noelia Hughes-Alford, Shannon Kay Tadros, Jenny Rudina, Shireen S. Hynes, Richard O. Lauffenburger, Douglas A. Gertler, Frank Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell–cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue “LERER” repeats. In fibroblasts, the Mena–α5 complex was required for “outside-in” α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins. National Institutes of Health (U.S.) (Grant GM58801) National Cancer Institute (U.S.) (Grant U54-CA112967) Howard Hughes Medical Institute 2012-11-19T17:23:21Z 2012-11-19T17:23:21Z 2012-08 2012-02 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/74675 Gupton, S. L. et al. “Mena binds α5 integrin directly and modulates α5β1 function.” The Journal of Cell Biology 198.4 (2012): 657–676. © 2012 by The Rockefeller University Press https://orcid.org/0000-0003-3214-4554 https://orcid.org/0000-0002-3048-7927 https://orcid.org/0000-0001-7603-8396 en_US http://dx.doi.org/10.1083/jcb.201202079 Journal of Cell Biology Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press, The Rockefeller UP |
| spellingShingle | Gupton, Stephanie L. Riquelme, Daisy Noelia Hughes-Alford, Shannon Kay Tadros, Jenny Rudina, Shireen S. Hynes, Richard O. Lauffenburger, Douglas A. Gertler, Frank Mena binds α5 integrin directly and modulates α5β1 function |
| title | Mena binds α5 integrin directly and modulates α5β1 function |
| title_full | Mena binds α5 integrin directly and modulates α5β1 function |
| title_fullStr | Mena binds α5 integrin directly and modulates α5β1 function |
| title_full_unstemmed | Mena binds α5 integrin directly and modulates α5β1 function |
| title_short | Mena binds α5 integrin directly and modulates α5β1 function |
| title_sort | mena binds α5 integrin directly and modulates α5β1 function |
| url | http://hdl.handle.net/1721.1/74675 https://orcid.org/0000-0003-3214-4554 https://orcid.org/0000-0002-3048-7927 https://orcid.org/0000-0001-7603-8396 |
| work_keys_str_mv | AT guptonstephaniel menabindsa5integrindirectlyandmodulatesa5b1function AT riquelmedaisynoelia menabindsa5integrindirectlyandmodulatesa5b1function AT hughesalfordshannonkay menabindsa5integrindirectlyandmodulatesa5b1function AT tadrosjenny menabindsa5integrindirectlyandmodulatesa5b1function AT rudinashireens menabindsa5integrindirectlyandmodulatesa5b1function AT hynesrichardo menabindsa5integrindirectlyandmodulatesa5b1function AT lauffenburgerdouglasa menabindsa5integrindirectlyandmodulatesa5b1function AT gertlerfrank menabindsa5integrindirectlyandmodulatesa5b1function |