Li, F, Abuarab, N and Sivaprasadarao, A orcid.org/0000-0002-6755-3502 (2016) Reciprocal regulation of actin cytoskeleton remodelling and cell migration by Ca2+ and Zn2+: role of TRPM2 channels. Journal of Cell Science, 129. pp. 2016-2029. ISSN 0021-9533
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016. Published by The Company of Biologists Ltd. Reproduced in accordance with the publisher's self-archiving policy. |
Keywords: | Cell migration; TRPM2 channel; Actin cytoskeleton dynamics; Lysosomal trafficking; Focal adhesions; Ca2+; Zn2+ |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 Apr 2016 09:27 |
Last Modified: | 12 Sep 2018 02:42 |
Published Version: | https://doi.org/10.1242/jcs.179796 |
Status: | Published |
Publisher: | Company of Biologists |
Identification Number: | 10.1242/jcs.179796 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97657 |
Commentary/Response Threads
- Li, F, Abuarab, N and Sivaprasadarao, A Reciprocal regulation of actin cytoskeleton remodelling and cell migration by Ca2+ and Zn2+: role of TRPM2 channels. (deposited 05 Apr 2016 09:27) [Currently Displayed]