2.50
Hdl Handle:
http://hdl.handle.net/10033/106889
Title:
Rac1 regulates neuronal polarization through the WAVE complex.
Authors:
Tahirovic, Sabina; Hellal, Farida; Neukirchen, Dorothee; Hindges, Robert; Garvalov, Boyan K; Flynn, Kevin C; Stradal, Theresia E; Chrostek-Grashoff, Anna; Brakebusch, Cord; Bradke, Frank
Abstract:
Neuronal migration and axon growth, key events during neuronal development, require distinct changes in the cytoskeleton. Although many molecular regulators of polarity have been identified and characterized, relatively little is known about their physiological role in this process. To study the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1-deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo and in vitro. In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott-Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1-knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth.
Affiliation:
Axonal Growth and Regeneration Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
Citation:
Rac1 regulates neuronal polarization through the WAVE complex. 2010, 30 (20):6930-43 J. Neurosci.
Journal:
The Journal of neuroscience : the official journal of the Society for Neuroscience
Issue Date:
19-May-2010
URI:
http://hdl.handle.net/10033/106889
DOI:
10.1523/JNEUROSCI.5395-09.2010
PubMed ID:
20484635
Type:
Article
Language:
en
ISSN:
1529-2401
Appears in Collections:
Publications of RG Signalling and Motility (SIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorTahirovic, Sabinaen
dc.contributor.authorHellal, Faridaen
dc.contributor.authorNeukirchen, Dorotheeen
dc.contributor.authorHindges, Roberten
dc.contributor.authorGarvalov, Boyan Ken
dc.contributor.authorFlynn, Kevin Cen
dc.contributor.authorStradal, Theresia Een
dc.contributor.authorChrostek-Grashoff, Annaen
dc.contributor.authorBrakebusch, Corden
dc.contributor.authorBradke, Franken
dc.date.accessioned2010-06-28T08:50:24Z-
dc.date.available2010-06-28T08:50:24Z-
dc.date.issued2010-05-19-
dc.identifier.citationRac1 regulates neuronal polarization through the WAVE complex. 2010, 30 (20):6930-43 J. Neurosci.en
dc.identifier.issn1529-2401-
dc.identifier.pmid20484635-
dc.identifier.doi10.1523/JNEUROSCI.5395-09.2010-
dc.identifier.urihttp://hdl.handle.net/10033/106889-
dc.description.abstractNeuronal migration and axon growth, key events during neuronal development, require distinct changes in the cytoskeleton. Although many molecular regulators of polarity have been identified and characterized, relatively little is known about their physiological role in this process. To study the physiological function of Rac1 in neuronal development, we have generated a conditional knock-out mouse, in which Rac1 is ablated in the whole brain. Rac1-deficient cerebellar granule neurons, which do not express other Rac isoforms, showed impaired neuronal migration and axon formation both in vivo and in vitro. In addition, Rac1 ablation disrupts lamellipodia formation in growth cones. The analysis of Rac1 effectors revealed the absence of the Wiskott-Aldrich syndrome protein (WASP) family verprolin-homologous protein (WAVE) complex from the plasma membrane of knock-out growth cones. Loss of WAVE function inhibited axon growth, whereas overexpression of a membrane-tethered WAVE mutant partially rescued axon growth in Rac1-knock-out neurons. In addition, pharmacological inhibition of the WAVE complex effector Arp2/3 also reduced axon growth. We propose that Rac1 recruits the WAVE complex to the plasma membrane to enable actin remodeling necessary for axon growth.en
dc.language.isoenen
dc.subject.meshAngiopoietinsen
dc.subject.meshAnimalsen
dc.subject.meshAnimals, Newbornen
dc.subject.meshApoptosisen
dc.subject.meshAxonsen
dc.subject.meshBromodeoxyuridineen
dc.subject.meshCell Movementen
dc.subject.meshCell Proliferationen
dc.subject.meshCells, Cultureden
dc.subject.meshCerebellumen
dc.subject.meshCofilin 1en
dc.subject.meshEnzyme Inhibitorsen
dc.subject.meshEnzyme-Linked Immunosorbent Assayen
dc.subject.meshGrowth Conesen
dc.subject.meshKi-67 Antigenen
dc.subject.meshLuminescent Proteinsen
dc.subject.meshMiceen
dc.subject.meshMice, Knockouten
dc.subject.meshMutationen
dc.subject.meshNerve Tissue Proteinsen
dc.subject.meshNeuronsen
dc.subject.meshOrgan Culture Techniquesen
dc.subject.meshRNA Interferenceen
dc.subject.meshRNA, Small Interferingen
dc.subject.meshTransfectionen
dc.subject.meshWiskott-Aldrich Syndrome Protein Familyen
dc.subject.meshcdc42 GTP-Binding Proteinen
dc.subject.meshrac1 GTP-Binding Proteinen
dc.subject.meshrhoA GTP-Binding Proteinen
dc.titleRac1 regulates neuronal polarization through the WAVE complex.en
dc.typeArticleen
dc.contributor.departmentAxonal Growth and Regeneration Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.en
dc.identifier.journalThe Journal of neuroscience : the official journal of the Society for Neuroscienceen
This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.