A dominant negative receptor for specific secreted semaphorins is generated by deleting an extracellular domain from neuropilin-1.
Neuropilins have recently been characterized as receptors for secreted semaphorins. Here, we report the generation of a dominant negative form of neuropilin-1 by the deletion of one of its extracellular domains. Expression of this variant in cultured primary sympathetic neurons blocks the paralysis of growth cone motility normally induced by SEMA-3A (collapsin-1, semaphorin III, semaphorin D) and SEMA-3C (collapsin-3, semaphorin E) but not that induced by SEMA-3F (semaphorin IV). A truncated form of neuropilin-1 that is missing its cytoplasmic domain fails to act as a dominant negative receptor component. These results suggest that neuropilin-1 is a necessary component of receptor complexes for some, but not all, secreted semaphorin family members. Overexpression of dominant negative neuropilins should provide a powerful new method of blocking the functions of secreted semaphorins.
Renzi
M J
MJ
Department of Neurosciences, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6074, USA.
Feiner
L
L
Koppel
A M
AM
Raper
J A
JA
D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D005728:Ganglia, Sympathetic / Q000502:physiology; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009414:Nerve Growth Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D039942:Neuropilin-1; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D040121:Semaphorin-3A; D017384:Sequence Deletion; D014162:Transfection
D002352:Carrier Proteins; D006023:Glycoproteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C108639:SEMA3A protein, human; D040121:Semaphorin-3A; C099436:semaphorin IV; D039942:Neuropilin-1