title: The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.
abstract: The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.
authors.affiliation: Department of Biology, Queen's University, Kingston, Canada.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Mohamed
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Boudreau
authors.forename: Fabian P S
authors.initials: FP
authors.lastname: Yu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Ian D
authors.initials: ID
authors.lastname: Chin-Sang
mesh_terms: D000199:Actins / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000502:physiology*; D020439:Growth Cones / Q000502:physiology* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D008840:Microfilament Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010750:Phosphoproteins; D000098662:Vasodilator-Stimulated Phosphoprotein; C532812:wsp-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; C111040:vab-1 protein, C elegans