Department of Biochemistry, Boston University School of Medicine, 72 E. Concord Street, Boston, MA 02118, USA.
Traffic. 2011 Jun;12(6):665-71. doi: 10.1111/j.1600-0854.2011.01175.x. Epub 2011 Mar 15.
Translocation of Glut4 to the plasma membrane of fat and skeletal muscle cells is mediated by specialized insulin-responsive vesicles (IRVs), whose protein composition consists primarily of glucose transporter isoform 4 (Glut4), insulin-responsive amino peptidase (IRAP), sortilin, lipoprotein receptor-related protein 1 (LRP1) and v-SNAREs. How can these proteins find each other in the cell and form functional vesicles after endocytosis from the plasma membrane? We are proposing a model according to which the IRV component proteins are internalized into sorting endosomes and are delivered to the IRV donor compartment(s), recycling endosomes and/or the trans-Golgi network (TGN), by cellugyrin-positive transport vesicles. The cytoplasmic tails of Glut4, IRAP, LRP1 and sortilin play an important targeting role in this process. Once these proteins arrive in the donor compartment, they interact with each other via their lumenal domains. This facilitates clustering of the IRV proteins into an oligomeric complex, which can then be distributed from the donor membranes to the IRV as a single entity with the help of adaptors, such as Golgi-localized, gamma-adaptin ear-containing, ARF-binding (GGA).
将葡萄糖转运蛋白 4（Glut4）、胰岛素应答氨基肽酶（IRAP）、分选连接蛋白（sortilin）、脂蛋白受体相关蛋白 1（LRP1）和 v-SNAREs 等蛋白组成的特殊胰岛素反应性囊泡（IRVs）介导 Glut4 从脂肪和骨骼肌细胞向质膜易位。这些蛋白如何在细胞内相互寻找，并在从质膜内吞后形成功能性囊泡？我们提出了一个模型，根据该模型，IRV 组分蛋白被内吞到分选内体中，并通过细胞糖蛋白阳性转运小泡被递送至 IRV 供体区室（s）、再循环内体和/或高尔基复合体（TGN）。Glut4、IRAP、LRP1 和 sortilin 的细胞质尾巴在这个过程中起着重要的靶向作用。一旦这些蛋白到达供体区室，它们就通过腔域相互作用。这有助于将 IRV 蛋白聚集到寡聚复合物中，然后在衔接蛋白（如定位于高尔基体的 γ 衔接蛋白含有 ARF 结合结构域（GGA））的帮助下，将该复合物从供体膜分配到 IRV 中。
