Palacín Manuel, Kanai Yoshikatsu
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona and Parc Cientìfic de Barcelona, Avda. Diagonal 645, 08028, Barcelona, Spain.
Pflugers Arch. 2004 Feb;447(5):490-4. doi: 10.1007/s00424-003-1062-7. Epub 2003 May 6.
The heteromeric amino acid transporters (HATs) are composed of a light and a heavy subunit linked by a disulfide bridge. The heavy subunits are the SLC3 members (rBAT and 4F2hc), whereas the light subunits are members of the SLC7 family of amino acid transporters. SLC3 proteins are type II membrane glycoproteins (i.e., one single transmembrane domain and the C-terminus located outside the cell) with a bulky extracellular domain that shows homology with alpha-glucosidases. rBAT heterodimerizes with b(0,+)AT (SLC7A9) constituting the amino acid transport b(0,+), the main system responsible for the apical reabsorption of cystine in kidney. The defect in this system causes cystinuria, the most common primary inherited aminoaciduria. 4F2hc subserves various amino acid transport systems by dimerization with different SLC7 proteins. The main role of SLC3 proteins is to help routing of the holotransporter to the plasma membrane. A working model for the biogenesis of HATs based on recent data on the rBAT/b(0,+)AT heterodimeric complex is presented. 4F2hc is a multifunctional protein, and in addition to its role in amino acid transport, it may be involved in other cellular functions. Studies on two SLC7 members (Asc-2 and AGT1) demonstrate heterodimerization with unknown heavy subunits.
异源氨基酸转运体（HATs）由通过二硫键连接的一个轻亚基和一个重亚基组成。重亚基是SLC3成员（rBAT和4F2hc），而轻亚基是氨基酸转运体SLC7家族的成员。SLC3蛋白是II型膜糖蛋白（即一个单一的跨膜结构域且C末端位于细胞外），具有一个与α-葡萄糖苷酶显示同源性的庞大细胞外结构域。rBAT与b(0,+)AT（SLC7A9）异源二聚化，构成氨基酸转运体b(0,+)，这是负责肾脏中胱氨酸顶端重吸收的主要系统。该系统的缺陷会导致胱氨酸尿症，这是最常见的原发性遗传性氨基酸尿症。4F2hc通过与不同的SLC7蛋白二聚化来服务于各种氨基酸转运系统。SLC3蛋白的主要作用是帮助全转运体转运至质膜。基于最近关于rBAT/b(0,+)AT异源二聚体复合物的数据，提出了一个HATs生物发生的工作模型。4F2hc是一种多功能蛋白，除了在氨基酸转运中的作用外，它可能还参与其他细胞功能。对两个SLC7成员（Asc-2和AGT1）的研究表明它们与未知的重亚基异源二聚化。
