Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion.
The formation of axon trajectories requires integration of local adhesive interactions with directional information from attractive and repulsive cues. Here, we show that these two types of information are functionally integrated; activation of the transmembrane receptor Roundabout (Robo) by its ligand, the secreted repulsive guidance cue Slit, inactivates N-cadherin-mediated adhesion. Loss of N-cadherin-mediated adhesion is accompanied by tyrosine phosphorylation of beta-catenin and its loss from the N-cadherin complex, concomitant with the formation of a supramolecular complex containing Robo, Abelson (Abl) kinase and N-cadherin. Local formation of such a receptor complex is an ideal mechanism to steer the growth cone while still allowing adhesion and growth in other directions.
D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism*; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism*; D046911:Macromolecular Substances; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D010446:Peptide Fragments; D017434:Protein Structure, Tertiary / Q000502:physiology; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012160:Retina; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin; D000097905:Roundabout Proteins
D015820:Cadherins; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016315:Proto-Oncogene Proteins c-abl; D011971:Receptors, Immunologic; D015534:Trans-Activators; D051176:beta Catenin; D000097905:Roundabout Proteins; C495267:CTNNB1 protein, mouse; C120566:slit protein, vertebrate