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Nat Commun ; 5: 4532, 2014 Jul 30.
Article in English | MEDLINE | ID: mdl-25074242

ABSTRACT

Throughout life, new neurons generated in the ventricular-subventricular zone take the long journey to the olfactory bulb. The intracellular mechanisms that precisely control the neurons' migration speed, enabling their well-organized movement, remain unclear. Rho signalling is known to affect the morphology and movement of various cell types, including neurons. Here we identify Gem-interacting protein (Gmip), a RhoA-specific GTPase-activating protein, as a key factor in saltatory neuronal migration. RhoA is activated at the proximal leading process of migrating neurons, where Gmip is also localized and negatively regulates RhoA. Gmip controls the saltatory movement of neurons that regulate their migration speed and 'stop' positions in the olfactory bulb, thereby altering the neural circuitry. This study demonstrates that Gmip serves as a brake for the RhoA-mediated movement of neuronal somata, and highlights the significance of speed control in the well-organized neuronal migration and the maintenance of neuronal circuits in the postnatal brain.


Subject(s)
Brain/cytology , Brain/growth & development , Cell Movement/physiology , GTPase-Activating Proteins/metabolism , Neurons/physiology , Signal Transduction/physiology , rhoA GTP-Binding Protein/metabolism , Animals , Blotting, Western , Bromodeoxyuridine , Immunohistochemistry , Immunoprecipitation , Mass Spectrometry , Mice , Mice, Knockout , Microfilament Proteins/metabolism , Microscopy, Confocal , RNA Interference , Rats , Rats, Wistar , Statistics, Nonparametric , Time-Lapse Imaging , Vesicular Transport Proteins/metabolism
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