TY - JOUR
T1 - The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/abLIM
AU - Gitai, Zemer
AU - Yu, Timothy W.
AU - Lundquist, Erik A.
AU - Tessier-Lavigne, Marc
AU - Bargmann, Cornelia I.
N1 - Funding Information:
We thank Megan Dell and Gian Garriga for sharing results prior to publication; Scott Clark and the Caenorhabditis Genetics Center for nematode strains; Andrew Fire for vectors; Hai Nguyen and Joe Hill for technical support; and Carrie Adler, Andy Chang, Jesse Gray, Maria Gallegos, Joe Hao, Amanda Kahn, Steve McCarroll, Coleen Murphy, Kang Shen, Miri VanHoven, and Jen Zallen for helpful discussions and comments on the manuscript. Z.G. was a Howard Hughes Medical Institute predoctoral fellow; T.W.Y. was a MINDS predoctoral fellow and a UCSF MSTP student; and M.T.-L. and C.I.B. are Investigators with the Howard Hughes Medical Institute. This work was funded by the Howard Hughes Medical Institute.
PY - 2003/1/9
Y1 - 2003/1/9
N2 - Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function in endogenous unc-40 signaling. Our results indicate that Enabled functions in axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40 P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other. Thus, UNC-40 might act as a scaffold to deliver several independent signals to the actin cytoskeleton.
AB - Netrins promote axon outgrowth and turning through DCC/UNC-40 receptors. To characterize Netrin signaling, we generated a gain-of-function UNC-40 molecule, MYR::UNC-40. MYR::UNC-40 causes axon guidance defects, excess axon branching, and excessive axon and cell body outgrowth. These defects are suppressed by loss-of-function mutations in ced-10 (a Rac GTPase), unc-34 (an Enabled homolog), and unc-115 (a putative actin binding protein). ced-10, unc-34, and unc-115 also function in endogenous unc-40 signaling. Our results indicate that Enabled functions in axonal attraction as well as axon repulsion. UNC-40 has two conserved cytoplasmic motifs that mediate distinct downstream pathways: CED-10, UNC-115, and the UNC-40 P2 motif act in one pathway, and UNC-34 and the UNC-40 P1 motif act in the other. Thus, UNC-40 might act as a scaffold to deliver several independent signals to the actin cytoskeleton.
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U2 - 10.1016/S0896-6273(02)01149-2
DO - 10.1016/S0896-6273(02)01149-2
M3 - Article
C2 - 12526772
AN - SCOPUS:0037426990
SN - 0896-6273
VL - 37
SP - 53
EP - 65
JO - Neuron
JF - Neuron
IS - 1
ER -