A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons.
We tested the contribution of the small GTPase Rho and its downstream target p160ROCK during the early stages of axon formation in cultured cerebellar granule neurons. p160ROCK inhibition, presumably by reducing the stability of the cortical actin network, triggered immediate outgrowth of membrane ruffles and filopodia, followed by the generation of initial growth cone-ike membrane domains from which axonal processes arose. Furthermore, a potentiation in both the size and the motility of growth cones was evident, though the overall axon elongation rate remained stable. Conversely, overexpression of dominant active forms of Rho or ROCK was suggested to prevent initiation of axon outgrowth. Taken together, our data indicate a novel role for the Rho/ROCK pathway as a gate critical for the initiation of axon outgrowth and the control of growth cone dynamics.
Bito
H
H
Department of Pharmacology, Kyoto University of Faculty of Medicine, Japan. hbito@mfour.med.kyoto-u.ac.jp
Furuyashiki
T
T
Ishihara
H
H
Shibasaki
Y
Y
Ohashi
K
K
Mizuno
K
K
Maekawa
M
M
Ishizaki
T
T
Narumiya
S
S
D000199:Actins / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004268:DNA-Binding Proteins / Q000502:physiology; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D054461:Lim Kinases; D051379:Mice; D009474:Neurons / Q000502:physiology*; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D013379:Substrate Specificity; D054460:rho-Associated Kinases
D000199:Actins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011494:Protein Kinases; D054461:Lim Kinases; C515893:Limk1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases