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Updated: May 13, 2026
12:09
Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4
Published on: December 31, 2013
TRPM7 is regulated by halides through its kinase domain
Haijie Yu1, Zheng Zhang, Annette Lis
1Center for Biomedical Research, The Queen's Medical Center, 1301 Punchbowl St., Honolulu, HI 96813, USA.
Cellular and Molecular Life Sciences : CMLS
|March 9, 2013
Summary
Chloride and bromide ions inhibit the TRPM7 channel, a key regulator of cell growth, especially when combined with intracellular magnesium. This finding suggests TRPM7
Area of Science:
- Cellular physiology
- Ion channel function
- Molecular biology
Background:
- Transient receptor potential melastatin 7 (TRPM7) is a cation channel crucial for cell growth and proliferation.
- Cell volume changes during proliferation are regulated by TRPM7 activity, influenced by solutes like magnesium.
- The precise regulatory mechanisms of TRPM7, particularly during osmotic stress, remain incompletely understood.
Purpose of the Study:
- To investigate the role of chloride and related halides as negative feedback regulators of TRPM7.
- To elucidate the mechanism by which halides modulate TRPM7 activity.
- To explore the potential implications of TRPM7 regulation by halides in cancer cell proliferation.
Main Methods:
- Heterologous expression of TRPM7 to study inhibition by chloride and bromide.
- Electrophysiological recordings to assess TRPM7 channel activity.
- Investigation of TRPM7 inhibition in MCF-7 breast cancer cells, including the role of the sodium-iodide symporter (SLC5A5).
Main Results:
- Chloride and bromide inhibit TRPM7, particularly in synergy with intracellular magnesium ([Mg(2+)]i).
- This inhibition occurs via the ATP-binding site of the TRPM7 kinase domain and leads to irreversible channel inactivation.
- Iodide exhibits the strongest inhibitory effect on TRPM7 and reduces proliferation in MCF-7 cells by upregulating SLC5A5, enhancing iodide uptake.
Conclusions:
- Chloride acts as a significant modulator of TRPM7 during osmotic stress.
- TRPM7 is implicated as a molecular target contributing to the anti-proliferative effects of iodide accumulation in cancer cells.
- Halides, especially iodide, represent a novel class of TRPM7 regulators with potential therapeutic implications.
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