Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion.

RHEE, JINSEOL; MAHFOOZ, NAJMUS S.; CARLOS OSCAR ARREGUI; LILIEN, JACK; BALSAMO, JANNE; VANBERKUM, MARK F.A.

NATURE CELL BIOLOGY.

Macmillan Magazines Ltd

Año: 2002 vol. 4 p. 798 - 805

1465-7392

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 b-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.