Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK.
Division of Biosciences, University College London, London WC1E 6BT, UK.
Trends Cell Biol. 2020 Sep;30(9):705-719. doi: 10.1016/j.tcb.2020.05.007. Epub 2020 Jun 30.
Insulin stimulates glucose transport by triggering regulated delivery of intracellular vesicles containing the GLUT4 glucose transporter to the plasma membrane. This process is defective in diseases such as type 2 diabetes (T2DM). While studies in rodent cells have been invaluable in understanding GLUT4 traffic, evolutionary plasticity must be considered when extrapolating these findings to humans. Recent work has identified species-specific distinctions in GLUT4 traffic, notably the participation of a novel clathrin isoform, CHC22, in humans but not rodents. Here, we discuss GLUT4 sorting in different species and how studies of CHC22 have identified new routes for GLUT4 trafficking. We further consider how different sorting-protein complexes relate to these routes and discuss other implications of these pathways in cell biology and disease.
胰岛素通过触发含有 GLUT4 葡萄糖转运体的细胞内囊泡的有调节的递送到质膜，从而刺激葡萄糖转运。在 2 型糖尿病 (T2DM) 等疾病中，这一过程存在缺陷。虽然啮齿动物细胞的研究对于理解 GLUT4 运输非常有价值，但在将这些发现推断到人类时，必须考虑进化的可塑性。最近的工作已经确定了 GLUT4 运输中的物种特异性差异，特别是在人类中但不在啮齿动物中参与一种新型网格蛋白同工型 CHC22。在这里，我们讨论了不同物种中的 GLUT4 分拣以及 CHC22 的研究如何确定了 GLUT4 运输的新途径。我们进一步考虑了不同分拣蛋白复合物与这些途径的关系，并讨论了这些途径在细胞生物学和疾病中的其他影响。
