Myosin IIA is required for neurite outgrowth inhibition produced by repulsive guidance molecule |
| |
Authors: | Kubo Takekazu Endo Mitsuharu Hata Katsuhiko Taniguchi Junko Kitajo Keiko Tomura Sayaka Yamaguchi Atsushi Mueller Bernhard K Yamashita Toshihide |
| |
Affiliation: | Department of Neurobiology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan; BioClues Inc., Nihonbashi, Chuo-ku, Tokyo, Japan; CNS Research, Abbott GmbH and Company KG, Ludwigshafen, Germany |
| |
Abstract: | Although myelin-associated neurite outgrowth inhibitors express their effects through RhoA/Rho-kinase, the downstream targets of Rho-kinase remain unknown. We examined the involvement of myosin II, which is one of the downstream targets of Rho-kinase, by using blebbistatin – a specific myosin II inhibitor – and small interfering RNA targeting two myosin II isoforms, namely, MIIA and MIIB. We found that neurite outgrowth inhibition by repulsive guidance molecule (RGMa) was mediated via myosin II, particularly MIIA, in cerebellar granule neurons. RGMa induced myosin light chain (MLC) phosphorylation by a Rho-kinase-dependent mechanism. After spinal cord injury in rats, phosphorylated MLC in axons around the lesion site was up-regulated, and this effect depends on Rho-kinase activity. Further, RGMa-induced F-actin reduction in growth cones and growth cone collapse were mediated by MIIA. We conclude that Rho-kinase-dependent activation of MIIA via MLC phosphorylation induces F-actin reduction and growth cone collapse and the subsequent neurite retraction/outgrowth inhibition triggered by RGMa. |
| |
Keywords: | axon myosin II repulsive guidance molecule Rho Rho-kinase spinal cord injury |
本文献已被 PubMed 等数据库收录! |
|