or 
Receptor Family
Roundabout
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Summary

The roundabout (Robo) receptors are a family of recruiter receptors important for cell migration. Robo receptors share motifs with the immunoglobulin superfamily and orthologs exist in D. melanogaster and C. elegans. Multiple Robo genes have been described in mammals. Members of the Slit family are ligands for the Robo receptors. Robo receptors are essential for neuronal growth guidance (76, 77). In addition, Robo receptors are expressed in nonneuronal tissues where they also have roles in migration (78). The interaction between Slit-2 and Robo-1 is enhanced by cell-surface heparan sulfate (79). Following ligand binding, Robo recruits such signaling components as the Abelson (Abl) tyrosine kinase and its substrate Enabled (Ena) (Fig. 4). Abl antagonizes Robo signaling whereas Ena is required for Robo's repulsive action (80). The relative effect of each signaling component is dependent upon concomitant input from other signaling systems. Upon Slit binding, Robo also serves as a silencer of the Netrin repellant receptor, DCC, through direct interaction of their intracellular domains (81). Thus, the Robo family of receptors shows several features of signaling receptors: modulation of activity by additional extracellular factors or membrane-bound proteins, and crosstalk with other receptors.
Relevant reviews and publications:
76. A. S. Plump, L. Erskine, C. Sabatier, K. Brose, C. J. Epstein, C. S. Goodman, C. A. Mason, M. Tessier-Lavigne, Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 33, 219-232 (2002). 77. L. D. Hutson, C. B. Chien, Pathfinding and error correction by retinal axons: the role of astray/robo2. Neuron 33, 205-217 (2002). 78. J. Y. Wu, L. Feng, H. T. Park, N. Havlioglu, L. Wen, H. Tang, K. B. Bacon, Z. Jiang, X. Zhang, Y. Rao, The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature 410, 948-952 (2001). 79. H. Hu, Cell-surface heparan sulfate is involved in the repulsive guidance activities of Slit2 protein. Nat Neurosci 4, 695-701 (2001). 80. G. J. Bashaw, T. Kidd, D. Murray, T. Pawson, C. S. Goodman, Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor. Cell 101, 703-715 (2000). 81. E. Stein, M. Tessier-Lavigne, Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science 291, 1928-1938 (2001).
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