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.
authors.affiliation: 1] Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK [2].
authors.forename: Roberta
authors.initials: R
authors.lastname: Azzarelli
authors.affiliation: 1] Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK [2].
authors.forename: Emilie
authors.initials: E
authors.lastname: Pacary
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Ritu
authors.initials: R
authors.lastname: Garg
authors.affiliation: Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Garcez
authors.affiliation: Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: van den Berg
authors.affiliation: 1] Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK [2].
authors.forename: Philippe
authors.initials: P
authors.lastname: Riou
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, New York 10029, USA.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Friedel
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Division of Molecular Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002522:Chlorocebus aethiops; D031541:Fluorescence Resonance Energy Transfer; D017403:In Situ Hybridization; D051379:Mice; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; C519231:Plxnb2 protein, mouse; C513341:Rnd3 protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein