Distinct CED-10/Rac1 domains confer context-specific functions in development.
Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. In Caenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel...
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2018-09-01
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Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC6179291?pdf=render |
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author | Steffen Nørgaard Shuer Deng Wei Cao Roger Pocock |
author_facet | Steffen Nørgaard Shuer Deng Wei Cao Roger Pocock |
author_sort | Steffen Nørgaard |
collection | DOAJ |
description | Rac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. In Caenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel to control axon outgrowth and guidance. Here, we have identified a single glycine residue in the CED-10/Rac1 Switch 1 region that confers a non-redundant function in axon outgrowth but not guidance. Mutation of this glycine to glutamic acid (G30E) reduces GTP binding and inhibits axon outgrowth but does not affect other canonical CED-10 functions. This demonstrates previously unappreciated domain-specific functions within the CED-10 protein. Further, we reveal that when CED-10 function is diminished, the adaptor protein NAB-1 (Neurabin) and its interacting partner SYD-1 (Rho-GAP-like protein) can act as inhibitors of axon outgrowth. Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development. |
first_indexed | 2024-12-21T21:56:46Z |
format | Article |
id | doaj.art-8c7349b61e82468ea4a4ef19a373ff69 |
institution | Directory Open Access Journal |
issn | 1553-7390 1553-7404 |
language | English |
last_indexed | 2024-12-21T21:56:46Z |
publishDate | 2018-09-01 |
publisher | Public Library of Science (PLoS) |
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series | PLoS Genetics |
spelling | doaj.art-8c7349b61e82468ea4a4ef19a373ff692022-12-21T18:48:57ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-09-01149e100767010.1371/journal.pgen.1007670Distinct CED-10/Rac1 domains confer context-specific functions in development.Steffen NørgaardShuer DengWei CaoRoger PocockRac GTPases act as master switches to coordinate multiple interweaved signaling pathways. A major function for Rac GTPases is to control neurite development by influencing downstream effector molecules and pathways. In Caenorhabditis elegans, the Rac proteins CED-10, RAC-2 and MIG-2 act in parallel to control axon outgrowth and guidance. Here, we have identified a single glycine residue in the CED-10/Rac1 Switch 1 region that confers a non-redundant function in axon outgrowth but not guidance. Mutation of this glycine to glutamic acid (G30E) reduces GTP binding and inhibits axon outgrowth but does not affect other canonical CED-10 functions. This demonstrates previously unappreciated domain-specific functions within the CED-10 protein. Further, we reveal that when CED-10 function is diminished, the adaptor protein NAB-1 (Neurabin) and its interacting partner SYD-1 (Rho-GAP-like protein) can act as inhibitors of axon outgrowth. Together, we reveal that specific domains and residues within Rac GTPases can confer context-dependent functions during animal development.http://europepmc.org/articles/PMC6179291?pdf=render |
spellingShingle | Steffen Nørgaard Shuer Deng Wei Cao Roger Pocock Distinct CED-10/Rac1 domains confer context-specific functions in development. PLoS Genetics |
title | Distinct CED-10/Rac1 domains confer context-specific functions in development. |
title_full | Distinct CED-10/Rac1 domains confer context-specific functions in development. |
title_fullStr | Distinct CED-10/Rac1 domains confer context-specific functions in development. |
title_full_unstemmed | Distinct CED-10/Rac1 domains confer context-specific functions in development. |
title_short | Distinct CED-10/Rac1 domains confer context-specific functions in development. |
title_sort | distinct ced 10 rac1 domains confer context specific functions in development |
url | http://europepmc.org/articles/PMC6179291?pdf=render |
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