Abstract
Plexin-B1, Sema4D receptor, mediates retraction and extension signals in axon guidance by associating with PDZ-containing Rho guanine nucleotide exchange factors (PDZ-RhoGEFs) which can activate a small Rho GTPase RhoA. RhoA is implicated in spine formation by rearranging actin cytoskeleton. Exogenous application of Sema4D to cultured neurons caused activation of RhoA, increase of spine density and changes in spine shape. Sema4D-induced changes in spine density were blocked by either Rho-kinase (a downstream of RhoA, ROCK) inhibitor Y-27632 or by overexpression of plexin-B1 mutant lacking the C-terminus which no longer associates with PDZ-RhoGEFs. This study suggests that Sema4D-plexin-B1 play a crucial role in spine formation by regulating RhoA/ROCK pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / pharmacology
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Animals
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Cells, Cultured
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Dendritic Spines / drug effects*
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Dendritic Spines / physiology*
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Dendritic Spines / ultrastructure
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Disks Large Homolog 4 Protein
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Embryo, Mammalian
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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GTPase-Activating Proteins / physiology*
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Hippocampus / cytology
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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Mice
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Mutation / physiology
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Neurons / drug effects
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Neurons / physiology
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Neurons / ultrastructure*
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Pyridines / pharmacology
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Rats
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Receptors, Cell Surface / physiology*
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Semaphorins / pharmacology*
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Transfection
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rho GTP-Binding Proteins / metabolism*
Substances
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Amides
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Enzyme Inhibitors
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GTPase-Activating Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Plxnb1 protein, rat
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Pyridines
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Receptors, Cell Surface
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Sema4d protein, mouse
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Semaphorins
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Y 27632
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rho GTP-Binding Proteins