An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration

Roberta Azzarelli; Emilie Pacary; Ritu Garg; Patricia Garcez; Debbie van den Berg; Philippe Riou; Anne J Ridley; Roland H Friedel; Maddy Parsons; François Guillemot

doi:10.1038/ncomms4405

An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration

Roberta Azzarelli, Emilie Pacary, Ritu Garg, Patricia Garcez, Debbie van den Berg, Philippe Riou, Anne J Ridley, Roland H Friedel, Maddy Parsons, François Guillemot

Research output: Contribution to journal › Article (Academic Journal) › peer-review

53 Citations (Scopus)

Abstract

A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration.

Original language	English
Pages (from-to)	3405
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4405
Publication status	Published - 27 Feb 2014

Keywords

Animals
Blotting, Western
COS Cells
Cell Line, Tumor
Cell Movement
Cercopithecus aethiops
Cerebral Cortex
Fluorescence Resonance Energy Transfer
In Situ Hybridization
Mice
Microscopy, Confocal
Nerve Tissue Proteins
Neurons
Protein Binding
RNA Interference
rho GTP-Binding Proteins
rhoA GTP-Binding Protein
Journal Article
Research Support, Non-U.S. Gov't

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- School of Cellular and Molecular Medicine - Professor, Head of School
- Cancer
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title = "An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration",

abstract = "A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration.",

keywords = "Animals, Blotting, Western, COS Cells, Cell Line, Tumor, Cell Movement, Cercopithecus aethiops, Cerebral Cortex, Fluorescence Resonance Energy Transfer, In Situ Hybridization, Mice, Microscopy, Confocal, Nerve Tissue Proteins, Neurons, Protein Binding, RNA Interference, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, Journal Article, Research Support, Non-U.S. Gov't",

author = "Roberta Azzarelli and Emilie Pacary and Ritu Garg and Patricia Garcez and {van den Berg}, Debbie and Philippe Riou and Ridley, {Anne J} and Friedel, {Roland H} and Maddy Parsons and Fran{\c c}ois Guillemot",

year = "2014",

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doi = "10.1038/ncomms4405",

language = "English",

volume = "5",

pages = "3405",

journal = "Nature Communications",

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T1 - An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration

AU - Azzarelli, Roberta

AU - Pacary, Emilie

AU - Garg, Ritu

AU - Garcez, Patricia

AU - van den Berg, Debbie

AU - Riou, Philippe

AU - Ridley, Anne J

AU - Friedel, Roland H

AU - Parsons, Maddy

AU - Guillemot, François

PY - 2014/2/27

Y1 - 2014/2/27

N2 - A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration.

AB - A transcriptional programme initiated by the proneural factors Neurog2 and Ascl1 controls successive steps of neurogenesis in the embryonic cerebral cortex. Previous work has shown that proneural factors also confer a migratory behaviour to cortical neurons by inducing the expression of the small GTP-binding proteins such as Rnd2 and Rnd3. However, the directionality of radial migration suggests that migrating neurons also respond to extracellular signal-regulated pathways. Here we show that the Plexin B2 receptor interacts physically and functionally with Rnd3 and stimulates RhoA activity in migrating cortical neurons. Plexin B2 competes with p190RhoGAP for binding to Rnd3, thus blocking the Rnd3-mediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity. Thus, an interaction between the cell-extrinsic Plexin signalling pathway and the cell-intrinsic Ascl1-Rnd3 pathway determines the level of RhoA activity appropriate for cortical neuron migration.

KW - Animals

KW - Blotting, Western

KW - COS Cells

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cercopithecus aethiops

KW - Cerebral Cortex

KW - Fluorescence Resonance Energy Transfer

KW - In Situ Hybridization

KW - Mice

KW - Microscopy, Confocal

KW - Nerve Tissue Proteins

KW - Neurons

KW - Protein Binding

KW - RNA Interference

KW - rho GTP-Binding Proteins

KW - rhoA GTP-Binding Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms4405

DO - 10.1038/ncomms4405

M3 - Article (Academic Journal)

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SN - 2041-1723

VL - 5

SP - 3405

JO - Nature Communications

JF - Nature Communications

ER -

An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration

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