Plexin-B1 is a GTPase activating protein for M-Ras, remodelling dendrite morphology.
Plexins are receptors for axonal guidance molecules known as semaphorins. We recently reported that the semaphorin 4D (Sema4D) receptor, Plexin-B1, induces axonal growth cone collapse by functioning as an R-Ras GTPase activating protein (GAP). Here, we report that Plexin-B1 shows GAP activity for M-Ras, another member of the Ras family of GTPases. In cortical neurons, the expression of M-Ras was upregulated during dendritic development. Knockdown of endogenous M-Ras-but not R-Ras-reduced dendritic outgrowth and branching, whereas overexpression of constitutively active M-Ras, M-Ras(Q71L), enhanced dendritic outgrowth and branching. Sema4D suppressed M-Ras activity and reduced dendritic outgrowth and branching, but this reduction was blocked by M-Ras(Q71L). M-Ras(Q71L) stimulated extracellular signal-regulated kinase (ERK) activation, inducing dendrite growth, whereas Sema4D suppressed ERK activity and down-regulation of ERK was required for a Sema4D-induced reduction of dendrite growth. Thus, we conclude that Plexin-B1 is a dual functional GAP for R-Ras and M-Ras, remodelling axon and dendrite morphology, respectively.
Saito
Yasuhiro
Y
Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Oinuma
Izumi
I
Fujimoto
Satoshi
S
Negishi
Manabu
M
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000201:enzymology*; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface; D039961:Semaphorins; D048049:Extracellular Signal-Regulated MAP Kinases; D020558:GTP Phosphohydrolases; C491617:Mras protein, rat; D020559:Monomeric GTP-Binding Proteins