Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.
In Drosophila, plexin A is a functional receptor for semaphorin-1a. Here we show that the human plexin gene family comprises at least nine members in four subfamilies. Plexin-B1 is a receptor for the transmembrane semaphorin Sema4D (CD100), and plexin-C1 is a receptor for the GPI-anchored semaphorin Sema7A (Sema-K1). Secreted (class 3) semaphorins do not bind directly to plexins, but rather plexins associate with neuropilins, coreceptors for these semaphorins. Plexins are widely expressed: in neurons, the expression of a truncated plexin-A1 protein blocks axon repulsion by Sema3A. The cytoplasmic domain of plexins associates with a tyrosine kinase activity. Plexins may also act as ligands mediating repulsion in epithelial cells in vitro. We conclude that plexins are receptors for multiple (and perhaps all) classes of semaphorins, either alone or in combination with neuropilins, and trigger a novel signal transduction pathway controlling cell repulsion.
Tamagnone
L
L
Institute for Cancer Research and Treatment, University of Torino, Candiolo, Italy. Itamagnone@ircc.unito.it
Artigiani
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Chen
H
H
He
Z
Z
Ming
G I
GI
Song
H
H
Chedotal
A
A
Winberg
M L
ML
Goodman
C S
CS
Poo
M
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Tessier-Lavigne
M
M
Comoglio
P M
PM
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D018715:Microscopy, Video; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D039942:Neuropilin-1; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D014714:Vertebrates; D014981:Xenopus
D017261:Glycosylphosphatidylinositols; D009419:Nerve Tissue Proteins; C492116:PLXNA1 protein, human; C492119:PLXNB1 protein, human; C492114:Plxna1 protein, mouse; C492113:Plxna2 protein, mouse; C492112:Plxna3 protein, mouse; C492110:Plxna4 protein, mouse; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; D039942:Neuropilin-1; D014443:Tyrosine; D019859:Proto-Oncogene Proteins c-met