期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 10, 页码 2016-2029出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.179796
关键词
Cell migration; TRPM2 channel; Actin cytoskeleton dynamics; Lysosomal trafficking; Focal adhesion; Ca2+; Zn2+
类别
资金
- China Scholarship Council
- University of Leeds
- King Abdulaziz University of Saudi Arabia for Health Sciences, Ministry of Higher Education for Saudi Arabia
Cell migration is a fundamental feature of tumour metastasis and angiogenesis. It is regulated by a variety of signalling molecules including H2O2 and Ca2+. Here, we asked whether the H2O2-sensitive transient receptor potential melastatin 2 (TRPM2) Ca2+ channel serves as a molecular link between H2O2 and Ca2+. H2O2-mediated activation of TRPM2 channels induced filopodia formation, loss of actin stress fibres and disassembly of focal adhesions, leading to increased migration of HeLa and prostate cancer (PC)-3 cells. Activation of TRPM2 channels, however, caused intracellular release of not only Ca2+ but also of Zn2+. Intriguingly, elevation of intracellular Zn2+ faithfully reproduced all of the effects of H2O2, whereas Ca2+ showed opposite effects. Interestingly, H2O2 caused increased trafficking of Zn2+-enriched lysosomes to the leading edge of migrating cells, presumably to impart polarisation of Zn2+ location. Thus, our results indicate that a reciprocal interplay between Ca2+ and Zn2+ regulates actin remodelling and cell migration; they call for a revision of the current notion that implicates an exclusive role for Ca2+ in cell migration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据