SRC-1 mediates UNC-5 signaling in Caenorhabditis elegans.
The secreted molecule unc-6/netrin is important for guiding axon projections and cell migrations. unc-5 and unc-40/DCC are identified as receptors for unc-6/netrin. The downstream factors of unc-6 receptors are beginning to be elucidated, and some key factors have been identified in various organisms. Here, we showed that SRC-1 interacts with the cytosolic domain of UNC-5 through its SH2 domain. This interaction also requires the intact kinase activity of SRC-1. Downregulation of src-1 by RNA interference decreases the biological processes initiated by the UNC-5 protein and decreases UNC-5 tyrosine phosphorylation. We also generated a chimeric protein consisting of the extracellular domain and transmembrane domain of UNC-5 and an intracellular domain of SRC-1. This fusion protein is able to partially rescue mutant phenotypes caused by unc-5 but not unc-6, unc-40, and unc-34. Our results support a model in which SRC-1 is required for UNC-5-induced axon repulsion and gonad migration signaling pathways and in which localizing SRC-1 activity to UNC-5 is crucial for proper signal transduction in response to unc-6/netrin.
Lee
Jeeyong
J
Life Sciences Institute, University of Michigan, 5450 Medical Science I Building, Ann Arbor, MI 48109-0606, USA.
Li
Weiquan
W
Guan
Kun-Liang
KL
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D002460:Cell Line; D005260:Female; D006801:Humans; D008297:Male; D010053:Ovary / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013737:Testis / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C077588:UNC-5 protein, C elegans; D014443:Tyrosine; D011494:Protein Kinases; C471235:SRC-1 protein, C elegans