Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA

• Published in: Nature communications Vol. 5; no. 1; p. 4532
• Main Authors: Ota, Haruko, Hikita, Takao, Sawada, Masato, Nishioka, Tomoki, Matsumoto, Mami, Komura, Masayuki, Ohno, Akihisa, Kamiya, Yukiyo, Miyamoto, Takuya, Asai, Naoya, Enomoto, Atsushi, Takahashi, Masahide, Kaibuchi, Kozo, Sobue, Kazuya, Sawamoto, Kazunobu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.07.2014; Nature Publishing Group
• Subjects: 13; 13/106; 13/51; 13/89; 14; 14/33; 14/63; 42; 631/378/2571; 631/80/84; 631/80/84/2341; 64; Animals; Blotting, Western; Brain - cytology; Brain - growth & development; Bromodeoxyuridine; Cell Movement - physiology; GTPase-Activating Proteins - metabolism; Humanities and Social Sciences; Immunohistochemistry; Immunoprecipitation; Mass Spectrometry; Mice; Mice, Knockout; Microfilament Proteins - metabolism; Microscopy, Confocal; multidisciplinary; Neurons - physiology; Rats; Rats, Wistar; rhoA GTP-Binding Protein - metabolism; RNA Interference; Science; Science (multidisciplinary); Signal Transduction - physiology; Statistics, Nonparametric; Time-Lapse Imaging; Vesicular Transport Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms5532

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. In the postnatal mouse brain, RhoA signalling regulates the saltatory movement of new neurons migrating from the ventricular–subventricular zone to the olfactory bulb. Here the authors show that a RhoA-specific GTPase-activating protein, Gmip, serves as a brake for RhoA-mediated saltatory movement of new neurons during migration.