The transmembrane protein Off-track associates with Plexins and functions downstream of Semaphorin signaling during axon guidance.
The Plexin family of transmembrane proteins appears to function as repulsive receptors for most if not all Semaphorins. Here, we use genetic and biochemical analysis in Drosophila to show that the transmembrane protein Off-track (OTK) associates with Plexin A, the receptor for Sema 1a, and that OTK is a component of the repulsive signaling response to Semaphorin ligands. In vitro, OTK associates with Plexins. In vivo, mutations in the otk gene lead to phenotypes resembling those of loss-of-function mutations of either Sema1a or PlexA. The otk gene displays strong genetic interactions with Sema1a and PlexA, suggesting that OTK and Plexin A function downstream of Sema 1a.
Winberg
M L
ML
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, 519 LSA, University of California, Berkeley, CA 94720, USA.
Tamagnone
L
L
Bai
J
J
Comoglio
P M
PM
Montell
D
D
Goodman
C S
CS
D000483:Alleles; D000818:Animals; D001369:Axons / Q000201:enzymology*; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D016373:DNA, Antisense; D004330:Drosophila; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011505:Protein-Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D039961:Semaphorins; D015398:Signal Transduction / Q000502:physiology*
D015816:Cell Adhesion Molecules, Neuronal; D016373:DNA, Antisense; D029721:Drosophila Proteins; D008024:Ligands; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D039961:Semaphorins; C116483:plexA protein, Drosophila; D011505:Protein-Tyrosine Kinases; C102667:htl protein, Drosophila