Distinct CED-10/Rac1 domains confer context-specific functions in development
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Distinct CED-10/Rac1 domains confer context-specific functions in development. / Nørgaard, Steffen; Deng, Shuer; Cao, Wei; Pocock, Roger.
In: P L o S Genetics, Vol. 14, No. 9, e1007670, 2018, p. 1-24.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Distinct CED-10/Rac1 domains confer context-specific functions in development
AU - Nørgaard, Steffen
AU - Deng, Shuer
AU - Cao, Wei
AU - Pocock, Roger
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pgen.1007670
DO - 10.1371/journal.pgen.1007670
M3 - Journal article
C2 - 30265669
AN - SCOPUS:85054589460
VL - 14
SP - 1
EP - 24
JO - P L o S Genetics
JF - P L o S Genetics
SN - 1553-7390
IS - 9
M1 - e1007670
ER -
ID: 204184030