2013 Fiscal Year Final Research Report

Novel regulatory mechanism of semaphorin in endosomal trafficking

Research Project

Project/Area Number	23390069
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	General medical chemistry
Research Institution	Osaka University
Principal Investigator	TOYOFUKU Toshihiko 大阪大学, 免疫学フロンティア研究センター, 准教授 (60322179)
Project Period (FY)	2011-04-01 – 2014-03-31
Keywords	セマフォリン / 網膜色素変性症 / 網膜色素上皮
Research Abstract	Sema4A was identified in a family suffering from retinitis pigmentosa (RP). We generated the Sema4A-deficient mice and found the degeneration of photoreceptors. This result supported the hypothesis that Sema4A is the one of the causative genes for the human retinitis pigmentosa. Retinal pigment epithelial cells (RPE), where Sema4A is expressed, prevent photoreceptors from light-induced apoptosis and support the retinoid recycling which regenerates the photo-converted retinoid to normal one. Sema4A was found to activate these processes through regulating the endosomal trafficking. We further generated the mice carrying the mutated Sema4A, which were identified in human RP and found that these mutations in Sema4A are responsible for the RP. The injection of retrovirus carrying wild-type Sema4A successfully rescued the defects in photoreceptors in mutated mice. This result provided the possibility that the RP can be improved by the gene-transfer of Sema4A into RPE.