TRPM2 | Transient Receptor Potential Cation Channel Subfamily M Member 2
Family:
Transient receptor potential channels
Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN
Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations
TRPM2: Background information
TRPM2 is a tetrameric cation channel that is permeable to calcium, sodium, and potassium. It is regulated by and is also activated by intracellular endogenous ligands and reactive oxygen species.
Gene:
TRPM2
Human Protein:
UniProt O94759
Tissue:
Brain, pancreas, spleen, kidney and a wide range of immunocytes, including lymphocytes, neutrophils, and monocytes/macrophages
Function/ Application:
TRPM2 is a thermosensitive channel which functions as ligand-gated ion channel. It mediates Sodium and Calcium influx into the cell, leading to increased cytoplasmic Calcium levels. TRPM2 contributes to Ca2+ release from intracellular stores in response to ADP-ribose. The ion channel plays a role in numerous processes that involve signaling via intracellular Ca2+ levels e.g. for the dendritic cell differentiation and maturation, and in dendritic cell chemotaxis or in the regulation of the reorganization of the actin cytoskeleton, or for the filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca2+ and Zn2+ levels. It participates in immunity and inflammation processes, insulin secretion and body temperature regulation.
Pathology:
Alzheimer's disease, auto inflammatory and metabolic diseases, such as gout, obesity and diabetes
Endogenous agonists/ antagonists:
ADPR and cyclic ADPR (cADPR) activate TRPM2. Furthermore pyridine dinucleotides bind to TRPM2 (which might be not involved in TRPM2 activation) including β-nicotinamide adenine dinucleotide (NAD), nicotinic acid adenine dinucleotide (NAAD) and NAAD-2’-phosphate (NAADP). TRPM2 is also activated by redox signals and its activation is involved in cell death induced by oxidative stress. Inactivated by intracellular ATP.
Interaction:
Calmodulin, EFHC1, PKCơ, PTPL1, Ras-related C3 botulinum toxin substrate 1 (Rac1), Polyubiquitin-C
Modulator:
Flufenamic Acid, Clotrimazole, Econazole
Assays:
Patch Clamp: whole cell, temperature control, intracellular solution exchange
Recommended Reviews:
International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003