MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin
Background: The cytoplasmic C. elegans protein MIG-10 affects cell migrations and is related to mammalian proteins that bind phospholipids and Ena/VASP actin regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia. Results: We show here...
| Main Authors: | , , , , , , |
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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/1721.1/83476 https://orcid.org/0000-0003-3214-4554 |
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| author | Chang, Chieh Adler, Carolyn E. Krause, Matthias Clark, Scott G. Tessier-Lavigne, Marc Bargmann, Cornelia I. Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chang, Chieh Adler, Carolyn E. Krause, Matthias Clark, Scott G. Tessier-Lavigne, Marc Bargmann, Cornelia I. Gertler, Frank |
| author_sort | Chang, Chieh |
| collection | MIT |
| description | Background:
The cytoplasmic C. elegans protein MIG-10 affects cell migrations and is related to mammalian proteins that bind phospholipids and Ena/VASP actin regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia.
Results:
We show here that during neuronal development, mig-10 and the C. elegans Ena/VASP homolog unc-34 cooperate to guide axons toward UNC-6 (netrin) and away from SLT-1 (Slit). The single mutants have relatively mild phenotypes, but mig-10; unc-34 double mutants arrest early in development with severe axon guidance defects. In axons that are guided toward ventral netrin, unc-34 is required for the formation of filopodia and mig-10 increases the number of filopodia. In unc-34 mutants, developing axons that lack filopodia are still guided to netrin through lamellipodial growth. In addition to its role in axon guidance, mig-10 stimulates netrin-dependent axon outgrowth in a process that requires the age-1 phosphoinositide-3 lipid kinase but not unc-34.
Conclusions:
mig-10 and unc-34 organize intracellular responses to both attractive and repulsive axon guidance cues. mig-10 and age-1 lipid signaling promote axon outgrowth; unc-34 and to a lesser extent mig-10 promote filopodia formation. Surprisingly, filopodia are largely dispensable for accurate axon guidance. |
| first_indexed | 2024-09-23T12:54:39Z |
| format | Article |
| id | mit-1721.1/83476 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:54:39Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/834762022-09-28T10:49:40Z MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin Chang, Chieh Adler, Carolyn E. Krause, Matthias Clark, Scott G. Tessier-Lavigne, Marc Bargmann, Cornelia I. Gertler, Frank Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Krause, Matthias Gertler, Frank Background: The cytoplasmic C. elegans protein MIG-10 affects cell migrations and is related to mammalian proteins that bind phospholipids and Ena/VASP actin regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia. Results: We show here that during neuronal development, mig-10 and the C. elegans Ena/VASP homolog unc-34 cooperate to guide axons toward UNC-6 (netrin) and away from SLT-1 (Slit). The single mutants have relatively mild phenotypes, but mig-10; unc-34 double mutants arrest early in development with severe axon guidance defects. In axons that are guided toward ventral netrin, unc-34 is required for the formation of filopodia and mig-10 increases the number of filopodia. In unc-34 mutants, developing axons that lack filopodia are still guided to netrin through lamellipodial growth. In addition to its role in axon guidance, mig-10 stimulates netrin-dependent axon outgrowth in a process that requires the age-1 phosphoinositide-3 lipid kinase but not unc-34. Conclusions: mig-10 and unc-34 organize intracellular responses to both attractive and repulsive axon guidance cues. mig-10 and age-1 lipid signaling promote axon outgrowth; unc-34 and to a lesser extent mig-10 promote filopodia formation. Surprisingly, filopodia are largely dispensable for accurate axon guidance. National Institutes of Health (U.S.) (Grant GM68678) Howard Hughes Medical Institute 2014-01-06T14:37:11Z 2014-01-06T14:37:11Z 2006-04 2006-03 Article http://purl.org/eprint/type/JournalArticle 09609822 1879-0445 http://hdl.handle.net/1721.1/83476 Chang, Chieh, Carolyn E. Adler, Matthias Krause, Scott G. Clark, Frank B. Gertler, Marc Tessier-Lavigne, and Cornelia I. Bargmann. “MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin.” Current Biology 16, no. 9 (May 2006): 854-862. Copyright © 2006 Elsevier Ltd. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1016/j.cub.2006.03.083 Current Biology 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 | Chang, Chieh Adler, Carolyn E. Krause, Matthias Clark, Scott G. Tessier-Lavigne, Marc Bargmann, Cornelia I. Gertler, Frank MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title | MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title_full | MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title_fullStr | MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title_full_unstemmed | MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title_short | MIG-10/Lamellipodin and AGE-1/PI3K Promote Axon Guidance and Outgrowth in Response to Slit and Netrin |
| title_sort | mig 10 lamellipodin and age 1 pi3k promote axon guidance and outgrowth in response to slit and netrin |
| url | http://hdl.handle.net/1721.1/83476 https://orcid.org/0000-0003-3214-4554 |
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