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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Main Authors: Steffen Nørgaard, Shuer Deng, Wei Cao, Roger Pocock
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-09-01
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.
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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
work_keys_str_mv AT steffennørgaard distinctced10rac1domainsconfercontextspecificfunctionsindevelopment
AT shuerdeng distinctced10rac1domainsconfercontextspecificfunctionsindevelopment
AT weicao distinctced10rac1domainsconfercontextspecificfunctionsindevelopment
AT rogerpocock distinctced10rac1domainsconfercontextspecificfunctionsindevelopment