Nck beta interacts with tyrosine-phosphorylated disabled 1 and redistributes in Reelin-stimulated neurons.
The tyrosine phosphorylation sites of the Disabled 1 (Dab1) docking protein are essential for the transmission of the Reelin signal, which regulates neuronal placement. Here we identify Nck beta as a phosphorylation-dependent, Dab1-interacting protein. The SH2 domain of Nck beta but not Nck alpha binds Dab1 phosphorylated on the Reelin-regulated site, Y220, or on Y232. Nck beta is coexpressed with Dab1 in the developing brain and in cultured neurons, where Reelin stimulation leads to the redistribution of Nck beta from the cell soma into neuronal processes. We found that tyrosine-phosphorylated Dab1 in synergy with Nck beta disrupts the actin cytoskeleton in transfected cells. In Drosophila melanogaster, exogenous expression of mouse Dab1 causes tyrosine phosphorylation site-dependent morphological changes in the compound eye. This phenotype is enhanced by overexpression of the Drosophila Nck protein Dock, suggesting a conserved interaction between the Disabled and Nck family members. We suggest a model in which Dab1 phosphorylation leads to the recruitment of Nck beta to the membrane, where it acts to remodel the actin cytoskeleton.
D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D000199:Actins; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; C080216:dab protein, Drosophila; D014443:Tyrosine; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases