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

Nature Cell Biology volume 4, pages 798–805 (2002)Cite this article

A Corrigendum to this article was published on 01 November 2002

Abstract

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 β-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.

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Figure 1: Activated Robo inhibits N-cadherin-mediated adhesion.
Figure 5: Deletion of the CC3 region of the Robo cytoplasmic domain restores N-cadherin function.
Figure 2: Slit inhibits retinal neurite extension on a substrate of N-cadherin.
Figure 3: Activated Robo results in hyperphosphorylation of β-catenin and dissociation of the cadherin–β-catenin bond.
Figure 4: Slit-activated full-length Robo or the cytoplasmic domain of Robo interacts with N-cadherin.
Figure 6: A cell-permeable peptide mimicking the CC3 domain blocks the effect of Slit.
Figure 7: The tyrosine kinase inhibitor AG957 reverses the effect of Slit on N-cadherin function.
Figure 8: Formation of the Robo–Abl–N-cadherin complex.

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Acknowledgements

We thank C. Goodman and M. Seeger for antibody and cDNA reagents and K. Campbell, D. Eberl and C.-F. Wu for careful reading of the manuscript. This work was supported by grants from the National Eye Institute (J.L. and J.B.) and the National Science Foundation (M.V.B.).

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Authors and Affiliations

  1. Department of Biological Sciences, The University of Iowa, Iowa City, 52242, IA, USA

    Jinseol Rhee, Carlos Arregui, Jack Lilien & Janne Balsamo

  2. Department of Biological Sciences, Wayne State University, Detroit, 48202, MI, USA

    Najmus S. Mahfooz & Mark F.A. VanBerkum

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Correspondence to Jack Lilien.

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Rhee, J., Mahfooz, N., Arregui, C. et al. Activation of the repulsive receptor Roundabout inhibits N-cadherin-mediated cell adhesion. Nat Cell Biol 4, 798–805 (2002). https://doi.org/10.1038/ncb858

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