Chimeric axon guidance receptors: the cytoplasmic domains of slit and netrin receptors specify attraction versus repulsion.
Frazzled (Fra) is the DCC-like Netrin receptor in Drosophila that mediates attraction; Roundabout (Robo) is a Slit receptor that mediates repulsion. Both ligands are expressed at the midline; both receptors have related structures and are often expressed by the same neurons. To determine if attraction versus repulsion is a modular function encoded in the cytoplasmic domain of these receptors, we created chimeras carrying the ectodomain of one receptor and the cytoplasmic domain of the other and tested their function in transgenic Drosophila. Fra-Robo (Fra's ectodomain and Robo's cytoplasmic domain) functions as a repulsive Netrin receptor; neurons expressing Fra-Robo avoid the Netrin-expressing midline and muscles. Robo-Fra (Robo's ectodomain and Fra's cytoplasmic domain) is an attractive Slit receptor; neurons and muscle precursors expressing Robo-Fra are attracted to the Slit-expressing midline.
Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
G J
GJ
Bashaw
C S
CS
Goodman
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D001665:Binding Sites; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D015870:Gene Expression; D019476:Insect Proteins / Q000378:metabolism; D008648:Mesoderm; D009132:Muscles / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075386:Netrin Receptors; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D000075386:Netrin Receptors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D000097905:Roundabout Proteins; C000617310:fra protein, Drosophila; C066819:sli protein, Drosophila