Production mechanism and functional role of myelin protein produced by stop codon readthrough

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500449
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: BABA Hiroko 東京薬科大学, 薬学部, 教授 (40271499)
• Co-Investigator(Renkei-kenkyūsha): YAMAGUCHI Yoshihide 東京薬科大学, 薬学部, 准教授 (50311832) ; HAYASHI Akiko 東京薬科大学, 薬学部, 講師 (90232090)
• Research Collaborator: NAKANISHI Hiroki ; YANO Noriko
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: リードスルー / ミエリン / 細胞接着 / リン酸化 / PKC

Outline of Final Research Achievements

L-MPZ is a novel isoform of myelin P0 that is produced from P0 mRNA by stop codon readthrough mechanism. Antibodies against L-MPZ are often found in the patient sera with peripheral neuropathy, but the role of the antibodies in neuropathy is unknown. In present study, production mechanism, function of L-MPZ in myelin, and relevance of the antibody to demyelination were examined. We found that rate of L-MPZ production (ratio of L-MPZ/P0) was dependent on the nucleotide sequence near the stop codon, and readthrough stimulating drug, G418, significantly elevated this ratio. L-MPZ showed cell adhesion activity in the transfected cells. Anti-L-MPZ antibody did not induce demyelination, but further study on its role in remyelination may be needed. Since cell adhesion activity of L-MPZ was weaker than that of P0, change of L-MPZ/P0 ratio may affect adherence of myelin layers. Thus, our study suggests that precausion should be needed when readthrough stimulating drugs are used for therapy.

Free Research Field

分子神経生物学