Kioumourtzoglou Dimitrios, Sadler Jessica B A, Black Hannah L, Berends Rebecca, Wellburn Cassie, Bryant Nia J, Gould Gwyn W
*Henry Wellcome Laboratory of Cell Biology, Institute for Molecular, Cell and Systems Biology, Davidson Building, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K.
†Department of Biology, University of York, Heslington, York YO10 5DD, U.K.
Biochem Soc Trans. 2014 Oct;42(5):1396-400. doi: 10.1042/BST20140114.
Insulin plays a fundamental role in whole-body glucose homeostasis. Central to this is the hormone's ability to rapidly stimulate the rate of glucose transport into adipocytes and muscle cells [1]. Upon binding its receptor, insulin stimulates an intracellular signalling cascade that culminates in redistribution of glucose transporter proteins, specifically the GLUT4 isoform, from intracellular stores to the plasma membrane, a process termed 'translocation' [1,2]. This is an example of regulated membrane trafficking [3], a process that also underpins other aspects of physiology in a number of specialized cell types, for example neurotransmission in brain/neurons and release of hormone-containing vesicles from specialized secretory cells such as those found in pancreatic islets. These processes invoke a number of intriguing biological questions as follows. How is the machinery involved in these membrane trafficking events mobilized in response to a stimulus? How do the signalling pathways that detect the external stimulus interface with the trafficking machinery? Recent studies of insulin-stimulated GLUT4 translocation offer insight into such questions. In the present paper, we have reviewed these studies and draw parallels with other regulated trafficking systems.
胰岛素在全身葡萄糖稳态中发挥着重要作用。其核心在于该激素能够迅速刺激葡萄糖转运进入脂肪细胞和肌肉细胞的速率[1]。胰岛素与其受体结合后,会刺激细胞内信号级联反应,最终导致葡萄糖转运蛋白,特别是GLUT4亚型,从细胞内储存部位重新分布到质膜,这一过程称为“转位”[1,2]。这是调节性膜运输的一个例子[3],该过程也是许多特殊细胞类型生理活动其他方面的基础,例如大脑/神经元中的神经传递以及来自特殊分泌细胞(如胰岛中的细胞)的含激素囊泡的释放。这些过程引发了一些有趣的生物学问题,如下所述。参与这些膜运输事件的机制是如何响应刺激而被动员起来的?检测外部刺激的信号通路如何与运输机制相互作用?最近关于胰岛素刺激的GLUT4转位的研究为这些问题提供了见解。在本文中,我们回顾了这些研究,并将其与其他调节性运输系统进行了比较。