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The Mg2+ and Mg(2+)-nucleotide-regulated channel-kinase TRPM7
1Laboratory of Cell and Molecular Signaling, The Queen's Medical Center, 1301 Punchbowl Street-UHT 8, Honolulu, HI 96813, USA.
Handbook of Experimental Pharmacology
|January 16, 2007
Summary
Transient Receptor Potential Melastatin 7 (TRPM7) is a vital ion channel essential for cell survival, regulating calcium and magnesium flux based on cellular energy levels. Its kinase domain plays a key role in this homeostatic mechanism.
Area of Science:
- Molecular Biology
- Cell Physiology
- Biophysics
Background:
- TRPM7 is a unique protein combining ion channel and kinase functions, crucial for cellular viability.
- It's a divalent cation-selective channel permeable to essential metals like Ca2+ and Mg2+.
- TRPM7 is constitutively active but regulated by intracellular Mg2+ and MgATP levels.
Purpose of the Study:
- To elucidate the regulatory mechanisms and physiological roles of the TRPM7 channel.
- To investigate the interplay between TRPM7's ion channel and kinase activities.
- To understand TRPM7's contribution to cellular homeostasis and its potential role in pathological conditions.
Main Methods:
- Electrophysiological recordings to characterize TRPM7 currents.
- Biochemical assays to study kinase activity and substrate phosphorylation.
- Cellular assays to assess the impact of TRPM7 on cell viability, adhesion, and proliferation.
Main Results:
- TRPM7 exhibits a nonlinear current-voltage relationship with outward rectification.
- Its activity is downregulated by Mg2+ and MgATP, and activated by reducing these regulators.
- TRPM7 activity is modulated by cAMP/PKA signaling, requiring its kinase domain.
- The kinase domain may phosphorylate substrates like annexin and myosin IIA heavy chain.
Conclusions:
- TRPM7 acts as a ubiquitous cellular sensor and regulator of Ca2+ and Mg2+ homeostasis, linked to the cell's metabolic state.
- Its dual ion channel and kinase functions are essential for maintaining cellular viability.
- TRPM7 plays a role in cell adhesion, growth, proliferation, and potentially cell death during stress like anoxia.
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