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The Journal of Neuroscience, September 15, 1999, 19(18):7870-7880
A Dominant Negative Receptor for Specific Secreted Semaphorins Is
Generated by Deleting an Extracellular Domain from Neuropilin-1
Michael J.
Renzi,
Leonard
Feiner,
Adam M.
Koppel, and
Jonathan A.
Raper
Department of Neurosciences, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104-6074
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.
Key words:
semaphorin; collapsin; neuropilin-1; sympathetic neuron; growth cone guidance; growth cone collapse; dominant negative
receptor
Copyright © 1999 Society for Neuroscience 0270-6474/99/19187870-11$05.00/0
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