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...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier B.V.
2012
|
| Online Access: | http://hdl.handle.net/1721.1/73488 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826208301294026752 |
|---|---|
| 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 employs 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 utilizes 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 utilized in other physiological contexts involving cell motility and
morphogenesis. |
| first_indexed | 2024-09-23T14:03:38Z |
| format | Article |
| id | mit-1721.1/73488 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:03:38Z |
| publishDate | 2012 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/734882022-10-01T18:53:48Z 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 Gertler, Frank Gupton, Stephanie L. 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 employs 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 utilizes 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 utilized in other physiological contexts involving cell motility and morphogenesis. Jane Coffin Childs Memorial Fund for Medical Research National Institutes of Health (U.S.) (NIH grant GM68678) Stanley Medical Research Institute 2012-09-28T18:09:32Z 2012-09-28T18:09:32Z 2010-05 Article http://purl.org/eprint/type/JournalArticle 1534-5807 1878-1551 http://hdl.handle.net/1721.1/73488 Gupton, Stephanie L., and Frank B. Gertler. “Integrin Signaling Switches the Cytoskeletal and Exocytic Machinery That Drives Neuritogenesis.” Developmental Cell 18.5 (2010): 725–736. Web. 20493807 https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/DOI 10.1016/j.devcel.2010.02.017 Developmental Cell Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier B.V. PMC |
| 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/1721.1/73488 https://orcid.org/0000-0003-3214-4554 |
| work_keys_str_mv | AT guptonstephaniel integrinsignalingswitchesthecytoskeletalandexocyticmachinerythatdrivesneuritogenesis AT gertlerfrank integrinsignalingswitchesthecytoskeletalandexocyticmachinerythatdrivesneuritogenesis |