TRPM2 Membrane Protein Introduction

Introduction of TRPM2

Transient receptor potential cation channel subfamily M member 2 (TRPM2), encoded by human gene TRPM2, is a calcium (Ca²⁺)-permeable non-selective cation channel belonging to the TRP ion channel family. TRPM2 has a wide expression in bone marrow, brain, spleen, placenta, lymph node, gallbladder, and many other tissues, and it has been detected in all hematopoietic cell lines, with weaker expression in primary human erythroblasts and HEK293 cells. TRPM2 shares the common structural features of TRPM channels, including an intracellular N and C termini, 6 transmembrane segments, and a pore region between segments 5 and 6.

Function of TRPM2 Membrane Protein

TRPM2 can form a tetrameric ion channel that is permeable to potassium, calcium, and sodium. The activity of TRPM2 is mediated by free intracellular ADP-ribose and can be enhanced by oxidative stress. It has been reported that TRPM2 is involved in oxidative stress-induced cell death and inflammation processes, as well as in lipopolysaccharide-provoked cytokine production. TRPM2 also plays a role in insulin secretion and regulates parts of the responses to TNF-α in the immune cells. TRPM2 is also involved in activation of NACHT, LRR and PYD domains-containing protein 3 inflammasomes (NALP3), the dysregulation of which may result in a number of metabolic and inflammatory diseases, such as diabetes, gout, and obesity. In the brain, aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. TRPM2 also has physiological functions in the brain, for example, it is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses.

Fig.1 Schematic model of TRPM2 involved in insulin secretion. (Yosida, 2014)

Application of TRPM2 Membrane Protein in Literature

1. Kheradpezhouh E., et al. Oxidative stress promotes redistribution of TRPM2 channels to the plasma membrane in hepatocytes. Biochem Biophys Res Commun. 2018, 503(3):1891-1896. PubMed ID: 30075844
   
   

   This article demonstrates that the transport of TRPM2 to the plasma membrane may potentially contribute to a positive feedback mechanism regulating calcium ion overload in hepatocytes under oxidative stress.

2. Sita G., et al. TRPM2 in the Brain: Role in Health and Disease. Cells. 2018, 7(7). pii: E82. PubMed ID: 30037128
   
   

   This article provides a brief review of the current understanding of TRPM2 functions in disease and health and discusses the future potential neuroprotective strategies about TRPM2.

3. Hirschler-Laszkiewicz I., et al. The Human Ion Channel TRPM2 Modulates Neuroblastoma Cell Survival and Mitochondrial Function through Pyk2, CREB, and MCU Activation. Am J Physiol Cell Physiol. 2018, 315(4):C571-C586. PubMed ID: 30020827
   
   

   This article confirms that the expression of TRPM2 can protect the neuroblastoma viability through Src, proline-rich tyrosine kinase 2, cAMP-response element binding protein and mitochondrial calcium uniporter activation, which play crucial roles in maintaining mitochondrial function and cellular bioenergetics.

4. Jiang L.H., et al. The TRPM2 channel nexus from oxidative damage to Alzheimer's pathologies: An emerging novel intervention target for age-related dementia. Ageing Res Rev. 2018, 47:67-79. PubMed ID: 30009973
   
   

   This article discusses the possibility of taking the TRPM2 ion channel as a novel therapeutic target for intervening age-related dementia and Alzheimer's disease.

5. Gao M., et al. Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca²⁺-dependent CaMKII/JNK cascade. Metabolism. 2018, 85:313-324. PubMed ID: 29775644
   
   

   This article confirms that TRPM2 may act as a positive regulator of adipocyte insulin resistance induced by angiotensin II through the Ca²⁺/CaMKII/JNK-dependent signaling pathway, suggesting that TRPM2 may be a novel therapeutic target to treat hypertension-associated insulin resistance.

TRPM2 Preparation Options

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Reference

1. Yosida M, et al. (2016). Involvement of cAMP/EPAC/TRPM2 activation in glucose- and incretin-induced insulin secretion. Diabetes. 63(10):3394-403.

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