Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin-2 receptors.
Neuropilin-1 (NP-1) has been identified as a necessary component of a semaphorin D (SemD) receptor that repulses dorsal root ganglion (DRG) axons during development. SemA and SemE are related to SemD and bind to NP-1, but do not repulse DRG axons. By expressing NP-1 in retinal neurons and NP-2 in DRG neurons, we demonstrate that neuropilins are sufficient to determine the functional specificity of semaphorin responsiveness. SemA and SemE block SemD binding to NP-1 and abolish SemD repulsion in axons expressing NP-1. SemA and SemE seem to have a newly discovered protein antagonist capacity at NP-1 receptors, whereas they act as agonists at receptors containing NP-2.
Takahashi
T
T
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nakamura
F
F
Jin
Z
Z
Kalb
R G
RG
Strittmatter
S M
SM
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo / Q000166:cytology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology*; D039942:Neuropilin-1; D012165:Retinal Ganglion Cells / Q000187:drug effects; D040121:Semaphorin-3A
D002352:Carrier Proteins; D006023:Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C108639:SEMA3A protein, human; C488217:Sema3a protein, mouse; D040121:Semaphorin-3A; C099435:semaphorin A(V); D039942:Neuropilin-1