マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2002
形態種別	学術論文
査読	査読あり
標題	Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes
執筆形態	共著
掲載誌名	Nature Genetics
掲載区分	国外
巻・号・頁	31(3),pp.320-325
著者・共著者	Shojiro Kikuchi, Masaki Hata, Kanehisa Fukumoto, Yukari Yamane, Takeshi Matsui, Atsushi Tamura, Shigenobu Yonemura, Hisakazu Yamagishi, Dietrich Keppler, Shoichiro Tsukita, Sachiko Tsukita
概要	The ezrin-radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs.