Role of ABCG5 and ABCG8 in Sterol Metabolism

这项资助的总体目标是确定ATP结合盒半转运蛋白， ABCG5和ABCG8（G5G8）介导固醇跨膜转运。此前我们 发现G5或G8中的突变导致谷甾醇血症，其特征是积累 植物甾醇和胆固醇的含量，以及过早的冠状动脉疾病。G5和G8必须 在运输至肝细胞的顶端表面之前在内质网（ER）中异源二聚化， 肠上皮细胞，其中转运蛋白分别分泌固醇进入胆汁和肠腔。在过去 在资助期间，我们开发了体内和体外试验，以评估G5G8的结构要求， 介导的固醇转运。

The overall goal of this grant is to determine the mechanism by which the ATP-binding cassette halftransporters, ABCG5 and ABCG8 (G5G8), mediate the transport of sterols across membranes. Previously, we discovered that mutations in either G5 or G8 cause sitosterolemia, which is characterized by the accumulation of plant sterols and cholesterol, and by premature coronary artery disease. We showed that G5 and G8 must heterodimerize in the endoplasmic reticulum (ER) prior to trafficking to the apical surfaces of hepatocytes and enterocytes, where the transporter secretes sterols into bile and the gut lumen, respectively. During the last funding period we developed in vivo and in vitro assays to assess the structural requirements for G5G8- mediated sterol transport.