Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function
Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled...
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| Format: | Article |
| Language: | en_US |
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American Society for Cell Biology
2014
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| Online Access: | http://hdl.handle.net/1721.1/90926 https://orcid.org/0000-0001-6738-2435 https://orcid.org/0000-0003-3214-4554 |
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| author | Barzik, Melanie McClain, Leslie Marie Gupton, Stephanie L. Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Barzik, Melanie McClain, Leslie Marie Gupton, Stephanie L. Gertler, Frank |
| author_sort | Barzik, Melanie |
| collection | MIT |
| description | Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP)–deficient MV[superscript D7] fibroblasts, which are also devoid of endogenous mDia2, as a model system to investigate how these different actin regulatory proteins affect filopodia morphology and dynamics independently of one another. Filopodia initiated by either Ena/VASP or mDia2 contained similar molecular inventory but differed significantly in parameters such as number, length, F-actin organization, lifetime, and protrusive persistence. Moreover, in the absence of Ena/VASP, filopodia generated by mDia2 did not support initiation of integrin-dependent signaling cascades required for adhesion and subsequent lamellipodial extension, thereby causing a defect in early cell spreading. Coexpression of VASP with constitutively active mDia2[superscript M/A] rescued these early adhesion defects. We conclude that Ena/VASP and mDia2 support the formation of filopodia with significantly distinct properties and that Ena/VASP regulates mDia2-initiated filopodial morphology, dynamics, and function. |
| first_indexed | 2024-09-23T13:26:14Z |
| format | Article |
| id | mit-1721.1/90926 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:26:14Z |
| publishDate | 2014 |
| publisher | American Society for Cell Biology |
| record_format | dspace |
| spelling | mit-1721.1/909262022-10-01T15:17:09Z Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function Barzik, Melanie McClain, Leslie Marie Gupton, Stephanie L. 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 Barzik, Melanie McClain, Leslie Marie Gertler, Frank Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP)–deficient MV[superscript D7] fibroblasts, which are also devoid of endogenous mDia2, as a model system to investigate how these different actin regulatory proteins affect filopodia morphology and dynamics independently of one another. Filopodia initiated by either Ena/VASP or mDia2 contained similar molecular inventory but differed significantly in parameters such as number, length, F-actin organization, lifetime, and protrusive persistence. Moreover, in the absence of Ena/VASP, filopodia generated by mDia2 did not support initiation of integrin-dependent signaling cascades required for adhesion and subsequent lamellipodial extension, thereby causing a defect in early cell spreading. Coexpression of VASP with constitutively active mDia2[superscript M/A] rescued these early adhesion defects. We conclude that Ena/VASP and mDia2 support the formation of filopodia with significantly distinct properties and that Ena/VASP regulates mDia2-initiated filopodial morphology, dynamics, and function. National Institutes of Health (U.S.) (Grant GM58801) National Cancer Institute (U.S.). Integrative Cancer Biology Program (Grant 1-U54-CA112967) 2014-10-14T20:34:44Z 2014-10-14T20:34:44Z 2014-07 2014-06 Article http://purl.org/eprint/type/JournalArticle 1059-1524 1939-4586 http://hdl.handle.net/1721.1/90926 Barzik, M., L. M. McClain, S. L. Gupton, and F. B. Gertler. “Ena/VASP Regulates mDia2-Initiated Filopodial Length, Dynamics, and Function.” Molecular Biology of the Cell 25, no. 17 (July 2, 2014): 2604–2619. https://orcid.org/0000-0001-6738-2435 https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1091/mbc.E14-02-0712 Molecular Biology of the Cell Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0 application/pdf American Society for Cell Biology American Society for Cell Biology |
| spellingShingle | Barzik, Melanie McClain, Leslie Marie Gupton, Stephanie L. Gertler, Frank Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title | Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title_full | Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title_fullStr | Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title_full_unstemmed | Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title_short | Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function |
| title_sort | ena vasp regulates mdia2 initiated filopodial length dynamics and function |
| url | http://hdl.handle.net/1721.1/90926 https://orcid.org/0000-0001-6738-2435 https://orcid.org/0000-0003-3214-4554 |
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