Comm sorts robo to control axon guidance at the Drosophila midline.
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.
Keleman
Krystyna
K
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Rajagopalan
Srikanth
S
Cleppien
Diana
D
Teis
David
D
Paiha
Karin
K
Huber
Lukas A
LA
Technau
Gerhard M
GM
Dickson
Barry J
BJ
D000818:Animals; D019556:COS Cells; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism / Q000637:transplantation; D004625:Embryo, Nonmammalian; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D007839:Functional Laterality / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D017434:Protein Structure, Tertiary / Q000235:genetics; D021381:Protein Transport / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C110665:comm protein, Drosophila