Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis
Neurons establish their unique morphology by elaborating multiple neurites that subsequently form axons and dendrites. Neurite initiation entails significant surface area expansion, necessitating addition to the plasma membrane. We report that regulated membrane delivery coordinated with the actin c...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/83934 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826200765781245952 |
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| author | Gupton, Stephanie L. Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Gupton, Stephanie L. Gertler, Frank |
| author_sort | Gupton, Stephanie L. |
| collection | MIT |
| description | Neurons establish their unique morphology by elaborating multiple neurites that subsequently form axons and dendrites. Neurite initiation entails significant surface area expansion, necessitating addition to the plasma membrane. We report that regulated membrane delivery coordinated with the actin cytoskeleton is crucial for neuritogenesis and identify two independent pathways that use distinct exocytic and cytoskeletal machinery to drive neuritogenesis. One pathway uses Ena/VASP-regulated actin dynamics coordinated with VAMP2-mediated exocytosis and involves a novel role for Ena/VASP in exocytosis. A second mechanism occurs in the presence of laminin through integrin-dependent activation of FAK and src and uses coordinated activity of the Arp2/3 complex and VAMP7-mediated exocytosis. We conclude that neuritogenesis can be driven by two distinct pathways that differentially coordinate cytoskeletal dynamics and exocytosis. These regulated changes and coordination of cytoskeletal and exocytic machinery may be used in other physiological contexts involving cell motility and morphogenesis. |
| first_indexed | 2024-09-23T11:41:24Z |
| format | Article |
| id | mit-1721.1/83934 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:41:24Z |
| publishDate | 2014 |
| publisher | Elsevier |
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| spelling | mit-1721.1/839342022-10-01T05:17:23Z Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis Gupton, Stephanie L. Gertler, Frank Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Gupton, Stephanie L. Gertler, Frank Neurons establish their unique morphology by elaborating multiple neurites that subsequently form axons and dendrites. Neurite initiation entails significant surface area expansion, necessitating addition to the plasma membrane. We report that regulated membrane delivery coordinated with the actin cytoskeleton is crucial for neuritogenesis and identify two independent pathways that use distinct exocytic and cytoskeletal machinery to drive neuritogenesis. One pathway uses Ena/VASP-regulated actin dynamics coordinated with VAMP2-mediated exocytosis and involves a novel role for Ena/VASP in exocytosis. A second mechanism occurs in the presence of laminin through integrin-dependent activation of FAK and src and uses coordinated activity of the Arp2/3 complex and VAMP7-mediated exocytosis. We conclude that neuritogenesis can be driven by two distinct pathways that differentially coordinate cytoskeletal dynamics and exocytosis. These regulated changes and coordination of cytoskeletal and exocytic machinery may be used in other physiological contexts involving cell motility and morphogenesis. Jane Coffin Childs Memorial Fund for Medical Research (Fellowship) National Institutes of Health (U.S.) (Grant GM68678) Stanley Medical Research Institute 2014-01-13T20:42:09Z 2014-01-13T20:42:09Z 2010-05 2010-01 Article http://purl.org/eprint/type/JournalArticle 15345807 1878-1551 http://hdl.handle.net/1721.1/83934 Gupton, Stephanie L., and Frank B. Gertler. “Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis.” Developmental Cell 18, no. 5 (May 2010): 725-736. Copyright © 2010 Elsevier Inc. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1016/j.devcel.2010.02.017 Developmental Cell 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 Elsevier Elsevier Open Archive |
| spellingShingle | Gupton, Stephanie L. Gertler, Frank Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title | Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title_full | Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title_fullStr | Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title_full_unstemmed | Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title_short | Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery that Drives Neuritogenesis |
| title_sort | integrin signaling switches the cytoskeletal and exocytic machinery that drives neuritogenesis |
| url | http://hdl.handle.net/1721.1/83934 https://orcid.org/0000-0003-3214-4554 |
| work_keys_str_mv | AT guptonstephaniel integrinsignalingswitchesthecytoskeletalandexocyticmachinerythatdrivesneuritogenesis AT gertlerfrank integrinsignalingswitchesthecytoskeletalandexocyticmachinerythatdrivesneuritogenesis |