title: Src inhibits midline axon crossing independent of Frazzled/Deleted in Colorectal Carcinoma (DCC) receptor tyrosine phosphorylation.
abstract: The phylogenetically conserved Netrin family of chemoattractants signal outgrowth and attractive turning of commissural axons through the Deleted in Colorectal Carcinoma (DCC) family of receptors. Src family kinases are thought to be major signaling effectors of Netrin/DCC. In vertebrates, Src and the closely related Fyn kinases phosphorylate DCC and form a receptor-bound signaling complex leading to activation of downstream effectors. Here we show that, in the Drosophila embryonic CNS, Src kinases are dispensable for midline attraction of commissural axons. Consistent with this observation, tyrosine phosphorylation of the Netrin receptor DCC or its Drosophila ortholog, Frazzled, is not necessary for attraction to Netrin. Moreover, we uncover an unexpected function of Src kinases: inhibition of midline axon crossing through a novel mechanism. We propose that distinct signaling outputs must exist for midline axon crossing independent of Src kinases in commissural neurons.
authors.affiliation: Cell and Molecular Biology Graduate Group and Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: O'Donnell
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Bashaw
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D020439:Growth Cones / Q000378:metabolism; D000075386:Netrin Receptors; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; C000617310:fra protein, Drosophila; D019061:src-Family Kinases