A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching
Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for ax...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press, The
2014
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| Online Access: | http://hdl.handle.net/1721.1/91533 https://orcid.org/0000-0001-6738-2435 |
| _version_ | 1826194687777570816 |
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| author | McClain, Leslie Marie Winkle, Cortney C. Valtschanoff, Juli G. Park, Charles S. Maglione, Christopher Gupton, Stephanie L. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering McClain, Leslie Marie Winkle, Cortney C. Valtschanoff, Juli G. Park, Charles S. Maglione, Christopher Gupton, Stephanie L. |
| author_sort | McClain, Leslie Marie |
| collection | MIT |
| description | Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion. |
| first_indexed | 2024-09-23T10:00:05Z |
| format | Article |
| id | mit-1721.1/91533 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:00:05Z |
| publishDate | 2014 |
| publisher | Rockefeller University Press, The |
| record_format | dspace |
| spelling | mit-1721.1/915332022-09-26T15:05:33Z A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching McClain, Leslie Marie Winkle, Cortney C. Valtschanoff, Juli G. Park, Charles S. Maglione, Christopher Gupton, Stephanie L. Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT McClain, Leslie Marie Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion. American Heart Association (Fellowship 0615692T) National Institutes of Health (U.S.) (Grant GM68678) 2014-11-12T14:14:16Z 2014-11-12T14:14:16Z 2014-04 2013-11 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/91533 Winkle, C. C., L. M. McClain, J. G. Valtschanoff, C. S. Park, C. Maglione, and S. L. Gupton. “A Novel Netrin-1-Sensitive Mechanism Promotes Local SNARE-Mediated Exocytosis During Axon Branching.” The Journal of Cell Biology 205, no. 2 (April 28, 2014): 217–232. https://orcid.org/0000-0001-6738-2435 en_US http://dx.doi.org/10.1083/jcb.201311003 Journal of Cell Biology Creative Commons Attribution http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Rockefeller University Press, The Rockefeller University Press |
| spellingShingle | McClain, Leslie Marie Winkle, Cortney C. Valtschanoff, Juli G. Park, Charles S. Maglione, Christopher Gupton, Stephanie L. A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title | A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title_full | A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title_fullStr | A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title_full_unstemmed | A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title_short | A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching |
| title_sort | novel netrin 1 sensitive mechanism promotes local snare mediated exocytosis during axon branching |
| url | http://hdl.handle.net/1721.1/91533 https://orcid.org/0000-0001-6738-2435 |
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