Noncanonical Notch function in motor axon guidance is mediated by Rac GTPase and the GEF1 domain of Trio.
The receptor Notch interacts with the Abl tyrosine kinase signaling pathway to control axon growth and guidance in Drosophila motor neurons. In part, this is mediated by binding to Trio, a guanine nucleotide exchange factor (GEF) for Rho GTPases. We show here that one of the two GEF domains of Trio, the Rac-specific GEF1, is essential for Trio-dependent motor axon guidance and for the genetic suppression of Notch function in motor axon patterning, but the Rho-specific GEF2 domain is not. Consistent with this, we show that Rac, and not Rho1 or Cdc42, interacts genetically with Notch in a manner indistinguishable from that of bona fide Abl signaling components. We infer, therefore, that Rac is a key component of Abl signaling in Drosophila motor axons, and specifically that it is the crucial Rho GTPase in "noncanonical" Notch/Abl signaling.
Axon Guidance and Neural Connectivity Unit, Basic Neuroscience Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Jeong K
JK
Song
Edward
E
Giniger
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002465:Cell Movement / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; D010750:Phosphoproteins; D051880:Receptors, Notch; D017346:Protein Serine-Threonine Kinases; C490974:trio protein, Drosophila; D020744:rac GTP-Binding Proteins
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