Comm Sorts Robo to Control Axon Guidance at the Drosophila Midline

• Published in: Cell Vol. 110; no. 4; pp. 415 - 427
• Main Authors: Keleman, Krystyna, Rajagopalan, Srikanth, Cleppien, Diana, Teis, David, Paiha, Karin, Huber, Lukas A., Technau, Gerhard M., Dickson, Barry J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-08-2002
• Subjects: Animals; Cell Communication - genetics; Cell Differentiation - genetics; Cell Membrane - genetics; Cell Membrane - metabolism; Central Nervous System - cytology; Central Nervous System - embryology; Central Nervous System - metabolism; COS Cells; Down-Regulation - genetics; Drosophila melanogaster - cytology; Drosophila melanogaster - embryology; Drosophila melanogaster - metabolism; Drosophila Proteins; Ectoderm - cytology; Ectoderm - metabolism; Ectoderm - transplantation; Embryo, Nonmammalian; Endosomes - genetics; Endosomes - metabolism; Functional Laterality - genetics; Gene Expression Regulation, Developmental - genetics; Graft Survival - genetics; Growth Cones - metabolism; Growth Cones - ultrastructure; Membrane Proteins - genetics; Membrane Proteins - metabolism; Models, Biological; Molecular Sequence Data; Nerve Tissue Proteins; Protein Structure, Tertiary - genetics; Protein Transport - genetics; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; Roundabout Proteins; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Stem Cell Transplantation; Stem Cells - cytology; Stem Cells - metabolism; Transport Vesicles - genetics; Transport Vesicles - metabolism
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00901-7

Axon growth across the
Drosophila midline requires Comm to downregulate Robo, the receptor for the midline repellent Slit. We show here that
comm is required in neurons, not in midline cells as previously thought, and that it is expressed specifically and transiently in commissural neurons. Comm acts as a sorting receptor for Robo, diverting it from the synthetic to the late endocytic pathway. A conserved cytoplasmic LPSY motif is required for endosomal sorting of Comm in vitro and for Comm to downregulate Robo and promote midline crossing in vivo. Axon traffic at the CNS midline is thus controlled by the intracellular trafficking of the Robo guidance receptor, which in turn depends on the precisely regulated expression of the Comm sorting receptor.