Mechanism of cellular localization of mutated creatine transporter toward therapy for creatine deficiency syndromes

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293035
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: Ohtsuki Sumio 熊本大学, その他の研究科, 教授 (60323036)
• Co-Investigator(Kenkyū-buntansha): 伊藤 慎悟 熊本大学, その他の研究科, 助教 (20466535) ; 和田 敬仁 京都大学, 医学(系)研究科(研究院), 准教授 (70359727)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: クレアチン / トランスポーター / 輸送 / クレアチン欠乏症 / 細胞内局在

Outline of Final Research Achievements

The purpose of the present research project was to clarify molecular mechanisms of abnormal intracellular localization of mutated human creatine transporter (CRT) for developing new therapeutic method for creatine deficiency syndromes. We analyzed G561R mutant of CRT, which we have been identified in Japanese patients. The mutation of G561R have been revealed to induce translocation of CRT from plasma membrane to intracellular membrane of the cultured cells. We have also identified that hCRT(G561R) had abnormal glycosylation. These results suggest that the functional impairment of hCRT(G561R) was caused by incomplete glycosylation due to misfolding during protein maturation, leading to changes of cellular localization.

Free Research Field

分子生物薬剤学