TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles

Sunday A. Abiria; Grigory Krapivinsky; Rajan Sah; Ana G. Santa-Cruz; Dipayan Chaudhuri; Jin Zhang; Pichet Adstamongkonkul; Paul G. Decaen; David E. Clapham

doi:10.1073/pnas.1707380114

TRPM7 senses oxidative stress to release Zn²⁺ from unique intracellular vesicles

Sunday A. Abiria, Grigory Krapivinsky, Rajan Sah, Ana G. Santa-Cruz, Dipayan Chaudhuri, Jin Zhang, Pichet Adstamongkonkul, Paul G. Decaen, David E. Clapham^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

90 Scopus citations

Abstract

TRPM7 (transient receptor potential cation channel subfamily M member 7) regulates gene expression and stress-induced cytotox-icity and is required in early embryogenesis through organ development. Here, we show that the majority of TRPM7 is localized in abundant intracellular vesicles. These vesicles (M7Vs) are distinct from endosomes, lysosomes, and other familiar vesicles or organelles. M7Vs accumulate Zn²⁺ in a glutathione-enriched, reduced lumen when cytosolic Zn²⁺ concentrations are elevated. Treatments that increase reactive oxygen species (ROS) trigger TRPM7-dependent Zn²+ release from the vesicles, whereas reduced glutathione prevents TRPM7-dependent cytosolic Zn²⁺ influx. These observations strongly support the notion that ROS-mediated TRPM7 activation releases Zn²⁺ from intracellular vesicles after Zn²⁺ overload. Like the endoplasmic reticulum, these vesicles are a distributed system for divalent cation uptake and release, but in this case the primary divalent ion is Zn²⁺ rather than Ca²⁺.

Original language	English (US)
Pages (from-to)	E6079-E6088
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	114
Issue number	30
DOIs	https://doi.org/10.1073/pnas.1707380114
State	Published - Jul 25 2017

Funding

We thank Maria Ericsson for EM, Clary Clish for metabolomics, Eric Spooner for proteomics studies, Bayush Dinegde for DNA purification, Svetlana Gapon for cell culture, and Luba Krapivinsky for TRPM7 antibody purification. This work was supported in part by NIH Institutional Research Training (T32) Grants 5T32HL007572-31 (to S.A.A.) and K99HL124070 (to D.C.) at Boston Children’s Hospital.

Keywords

TRPM7
Vesicles
Zinc

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1707380114

Cite this

Abiria, S. A., Krapivinsky, G., Sah, R., Santa-Cruz, A. G., Chaudhuri, D., Zhang, J., Adstamongkonkul, P., Decaen, P. G., & Clapham, D. E. (2017). TRPM7 senses oxidative stress to release Zn²⁺ from unique intracellular vesicles. Proceedings of the National Academy of Sciences of the United States of America, 114(30), E6079-E6088. https://doi.org/10.1073/pnas.1707380114

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