Regulation of basal autophagy by transient receptor potential melastatin 7 (TRPM7) channel
Regulation of basal autophagy by transient receptor potential melastatin 7 (TRPM7) channel
复制标题
DOI：
10.1016/j.bbrc.2015.05.007
复制
发表时间：
2015-07-17
影响因子：
3.1
通讯作者：
Chung, Sungkwon
中科院分区：
文献类型：
--
作者：
Oh, Hyun Geun;Chun, Yoon Sun;Chung, Sungkwon
巨噬细胞自噬(以下简称自噬)是细胞成分降解和循环的分解代谢过程。自噬消化细胞内的成分，回收物质随后用于新的蛋白质合成。在一些细胞中，钙离子和镁离子可穿透的瞬时受体潜能Melastatin 7(TRPM7)通道构成了钙离子内流的基础。由于自噬是由细胞内钙离子水平调节的，我们着手确定通过TRPM7通道的钙离子内流是否调节基础自噬。当在营养丰富的条件下诱导HEK293细胞表达TRPM7通道时，LC3-II水平增加，表明基础自噬水平增加。TRPM7通道对基础自噬的影响是通过钙/钙调蛋白依赖的蛋白激酶β和AMP激活的蛋白激酶途径实现的。相反，当SH-SY5Y细胞的内源性TRPM7通道被短发夹状RNA下调时，基础自噬水平降低。类似地，TRPM7通道的抑制剂降低了基础自噬的水平。此外，通道阻滞剂对基础自噬的抑制作用可被细胞外钙离子浓度升高所逆转，提示钙离子通过TRPM7通道的内流直接与基础自噬有关。因此，我们的研究证明了TRPM7通道介导的钙离子内流在基础自噬调节中的新作用。(C)2015 Elsevier Inc.保留所有权利。
Macroautophagy (hereafter referred to as autophagy) is a catabolic process for the degradation and recycling of cellular components. Autophagy digests intracellular components, recycling material subsequently used for new protein synthesis. The Ca2+- and Mg2+-permeable transient receptor potential melastatin 7 (TRPM7) channel underlies the constitutive Ca2+ influx in some cells. Since autophagy is regulated by cytosolic Ca2+ level, we set out to determine whether Ca2+ influx through the TRPM7 channel regulates basal autophagy. When TRPM7 channel expression was induced from HEK293 cells in a nutrient-rich condition, LC3-II level increased indicating the increased level of basal autophagy. The effect of TRPM7 channel on basal autophagy was via Ca2+/calmodulin-dependent protein kinase kinase beta, and AMP-activated protein kinase pathway. In contrast, the level of basal autophagy was decreased when the endogenous TRPM7 channel in SH-SY5Y cells was down-regulated using short hairpin RNA. Similarly, an inhibitor for TRPM7 channel decreased the level of basal autophagy. In addition, the inhibitory effect of channel inhibitor on basal autophagy was reversed by increasing extracellular Ca(2+)concentration, suggesting that Ca2+ influx through TRPM7 channel directly links to basal autophagy. Thus, our studies demonstrate the new role of TRPM7 channel-mediated Ca2+ entry in the regulation of basal autophagy. (C) 2015 Elsevier Inc. All rights reserved.