Department of Physiology, Tulane University Health Sciences Center and School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, United States.
Department of Physiology, Tulane University Health Sciences Center and School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, United States.
Cell Signal. 2019 Aug;60:17-30. doi: 10.1016/j.cellsig.2019.03.022. Epub 2019 Apr 3.
Endocytosis is a prominent clathrin-mediated mechanism for concentrated uptake and internalization of ligand-receptor complexes, also known as cargo. Internalization of cargo is the fundamental mechanism for receptor-dependent regulation of cell membrane function, intracellular signal transduction, and neurotransmission, as well as other biological and physiological activities. However, the intrinsic mechanisms of receptor endocytosis and contemporaneous intracellular signaling are not well understood. We review emerging concepts of receptor endocytosis with concurrent intracellular signaling, using a typical example of guanylyl cyclase/natriuretic peptide receptor-A (NPRA) internalization, subcellular trafficking, and simultaneous generation of second-messenger cGMP and signaling in intact cells. We highlight the role of short-signal motifs located in the carboxyl-terminal regions of membrane receptors during their internalization and subsequent receptor trafficking in organelles that are not traditionally studied in this context, including nuclei and mitochondria. This review sheds light on the importance of future investigations of receptor endocytosis and trafficking in live cells and intact animals in vivo in physiological context.
内吞作用是一种突出的网格蛋白介导的机制，用于浓缩摄取和内化配体-受体复合物，也称为货物。货物的内化是受体依赖性调节细胞膜功能、细胞内信号转导和神经递质传递以及其他生物和生理活动的基本机制。然而，受体内吞作用和同时发生的细胞内信号的内在机制尚不清楚。我们使用鸟苷酸环化酶/利钠肽受体-A（NPRA）内化、亚细胞运输以及完整细胞中二信使 cGMP 和信号的同时产生的典型例子，综述了受体内吞作用和同时发生的细胞内信号的新出现的概念。我们强调了位于膜受体羧基末端区域的短信号基序在其内化和随后在传统上不在此背景下研究的细胞器中的受体运输中的作用，包括细胞核和线粒体。这篇综述阐明了在生理环境中在活细胞和完整动物体内进行受体内吞作用和运输的未来研究的重要性。
