The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance

• Published in: PLoS genetics Vol. 8; no. 2; p. e1002513
• Main Authors: Mohamed, Ahmed M, Boudreau, Jeffrey R, Yu, Fabian P S, Liu, Jun, Chin-Sang, Ian D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2012; Public Library of Science (PLoS)
• Subjects: Actins - physiology; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Animals, Genetically Modified; Biology; Caenorhabditis elegans - cytology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cells; Cytoskeleton - physiology; Genetics; Growth Cones - physiology; Growth Cones - ultrastructure; Medical research; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Nematodes; Neurons - physiology; Neurons - ultrastructure; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Proteins; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Signal Transduction
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002513

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.