Open AccessReciprocal regulation of actin cytoskeleton remodelling and cell migration by calcium and zinc: role of TRPM2 channels
Author(s) -
Fangfang Li,
Nada Abuarab,
Asipu Sivaprasadarao
Publication year - 2016
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.179796
Subject(s) - biology , microbiology and biotechnology , filopodia , cell migration , actin , trpm2 , cytoskeleton , intracellular , actin cytoskeleton , calcium signaling , focal adhesion , transient receptor potential channel , cell , phosphorylation , biochemistry , receptor
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 if the H2O2-sensitive Transient Receptor Potential Melastatin 2 (TRPM2) calcium channel serves as a molecular link between H2O2 and Ca2+. H2O2 activation of TRPM2 channels induced filopodia formation, loss of actin stress fibres and disassembly of focal adhesions, leading to increased migration of HeLa and PC (prostate cancer)-3 cells. Activation of TRPM2 channels, however, caused intracellular release of not only Ca2+, but also Zn2+. Intriguingly, elevation of intracellular Zn2+ faithfully reproduced all of the effects of H2O2, while 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+. 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.