Identification and the physiological role of a cystine transporter

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Osaka University
• Principal Investigator: NAGAMORI Shushi 大阪大学, 医学(系)研究科(研究院), 准教授 (90467572)
• Co-Investigator(Kenkyū-buntansha): OHGAKI Ryuichi 大阪大学, 大学院医学系研究科, 助教 (20467525) ; NISHIZONO Hirofumi 富山大学, 生命科学先端研究センター, 助教 (10502289)
• Co-Investigator(Renkei-kenkyūsha): KANAI Yoshikatsu 大阪大学, 大学院医学系研究科, 教授 (60204533)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: シスチン尿症 / アミノ酸トランスポーター / 腎臓 / ヘテロダイマー

Outline of Final Research Achievements

The heterodimeric amino acids transporter (HAT) family, which consists of heavy chains (Slc3) and light chains (Slc7), has important roles for amino acid transports in many types of organs. Among the family, rBAT forms a heterodimeric complex only with b0,+AT. Mutations in the two genes cause cystinuria, an autosomal recessive disorder of renal reabsorption of cystine at the apical membranes of proximal tubules. However, the expression paradox of the proteins has been remaining. While rBAT highly express in the S3 segment of the proximal tubules, the expression of b0,+AT decrease from the S1 to the S3 segment. In this study, Slc7a13, one of the HAT family members with an unknown heavy chain, was found to form a heterodimer with rBAT. Slc7a13 was expressed dominantly in the S3 segment and transported cystine. These findings strongly indicate that Slc7a13 is the secondary cystine transporter at the S3 segment in the kidney, which was postulated the presence in 70’s.

Free Research Field

膜タンパク質の生化学