Trpm2

Abstract

TRPM2 is the second member of the transient receptor potential melastatin-related (TRPM) family of cation channels. The protein is widely expressed including in the brain, immune system, endocrine cells, and endothelia. It embodies both ion channel functionality and enzymatic ADP-ribose (ADPr) hydrolase activity. TRPM2 is a Ca(2+)-permeable nonselective cation channel embedded in the plasma membrane and/or lysosomal compartments that is primarily activated in a synergistic fashion by intracellular ADP-ribose (ADPr) and Ca(2+). It is also activated by reactive oxygen and nitrogen species (ROS/NOS) and enhanced by additional factors, such as cyclic ADPr and NAADP, while inhibited by permeating protons (acidic pH) and adenosine monophosphate (AMP). Activation of TRPM2 leads to increases in intracellular Ca(2+) levels, which can serve signaling roles in inflammatory and secretory cells through release of vesicular mediators (e.g., cytokines, neurotransmitters, insulin) and in extreme cases can induce apoptotic and necrotic cell death under oxidative stress.

Negatively Charged Amino Acids Near and in Transient Receptor Potential (TRP) Domain of TRPM4 Channel Are One Determinant of Its Ca2+ Sensitivity

“…Involvements of the comparable aspartate and glutamate of TRPM5 in its activation by Ca 2ϩ should be addressed. TRPM2 is activated in a synergistic fashion by intracellular ADP-ribose and Ca 2ϩ (48). It has been reported that the mutation of the calmodulinbinding domain, located in the N terminus of TRPM2, made the channel nonfunctional (49).…”

Depletion of the Human Ion Channel TRPM2 in Neuroblastoma Demonstrates Its Key Role in Cell Survival through Modulation of Mitochondrial Reactive Oxygen Species and Bioenergetics

“…The second member of this subfamily to be cloned, TRPM2, is a 1503-amino acid channel permeable to Ca 2ϩ , Na ϩ , and K ϩ (6) and is widely expressed in many cell types including brain, hematopoietic cells, heart, and endothelial cells (7,8). Its role in normal physiological conditions as well as in oxidative stress is under investigation in many cell types (9). Oxidative stress, TNF␣, and amyloid ␤-peptide are among the key extracellular signals known to activate TRPM2 (10 -13).…”

A Splice Variant of the Human Ion Channel TRPM2 Modulates Neuroblastoma Tumor Growth through Hypoxia-inducible Factor (HIF)-1/2α

“…TRPM2 channels are permeable to Ca 2ϩ , Na ϩ , and K ϩ and are widely expressed in many cell types including brain, hema-topoietic cells, heart, vascular smooth muscle, and endothelial cells (7,8). The role of TRPM2 in numerous cell types including brain, heart, endothelial cells, and inflammatory cells under physiological conditions as well as oxidative stress is actively being investigated (9). Extracellular signals that activate TRPM2 include oxidative stress, TNF␣, and amyloid ␤-peptide (10 -13).…”