Neogenin mediates the action of repulsive guidance molecule.
Repulsive guidance molecule (RGM) is a recently identified protein implicated in both axonal guidance and neural tube closure. The avoidance of chick RGM in the posterior optic tectum by growing temporal, but not nasal, retinal ganglion cell axons is thought to contribute to visual map formation. In contrast to ephrins, semaphorins, netrins and slits, no receptor mechanism for RGM action has been defined. Here, an expression cloning strategy identified neogenin as a binding site for RGM, with a sub-nanomolar affinity. Consistent with selective axonal responsiveness to RGM, neogenin is expressed in a gradient across the chick retina. Neogenin is known to be one of several netrin-binding proteins but only neogenin interacts with RGM. The avoidance of RGM by temporal retinal axons is blocked by the anti-neogenin antibody and the soluble neogenin ectodomain. Dorsal root ganglion axons are unresponsive to RGM but are converted to a responsive state by neogenin expression. Thus, neogenin functions as an RGM receptor.
Rajagopalan
Srikanth
S
Department of Neurology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Deitinghoff
Lutz
L
Davis
Denise
D
Conrad
Sabine
S
Skutella
Thomas
T
Chedotal
Alain
A
Mueller
Bernhard K
BK
Strittmatter
Stephen M
SM
D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism
D030161:Avian Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C091279:neogenin