An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and cortical neuron migration.
Nat Commun. 2014-02-27; 5(1):
Lire sur PubMed
1. Nat Commun. 2014 Feb 27;5:3405. doi: 10.1038/ncomms4405.
An antagonistic interaction between PlexinB2 and Rnd3 controls RhoA activity and
cortical neuron migration.
Azzarelli R(1), Pacary E(1), Garg R(2), Garcez P(3), van den Berg D(3), Riou
P(4), Ridley AJ(2), Friedel RH(5), Parsons M(2), Guillemot F(3).
(1)1] Division of Molecular Neurobiology, MRC National Institute for Medical
Research, Mill Hill, London NW7 1AA, UK .
(2)Randall Division of Cell and Molecular Biophysics, King’s College London,
London SE1 1UL, UK.
(3)Division of Molecular Neurobiology, MRC National Institute for Medical
Research, Mill Hill, London NW7 1AA, UK.
(4)1] Randall Division of Cell and Molecular Biophysics, King’s College London,
London SE1 1UL, UK .
(5)Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425
Madison Avenue, New York, New York 10029, USA.
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.
PMID: 24572910 [Indexed for MEDLINE]