Laboratory of Ion Channel Research

The TRPM subfamily, named after the tumor suppressor melastatin (TRPM1), contains eight mammalian members. TRPM channels lack ankyrin repeats in the N-terminus, but contain the TRP domain in the C-terminus. The C-terminus of TRPM proteins is considerably longer than the corresponding region of other TRPs. The C-terminus of several members contains enzyme domains (“chanzymes”).

• TRPM1 or melastatin is a tumor suppressor protein isolated in a screen for genes whose level of expression (inversely) correlated with the severity of metastatic potential of a melanoma cell line.
• TRPM2 is a Ca²⁺-permeable channel that contains an ineffective C-terminal ADP-ribose pyrophosphatase domain that binds ADP-ribose and NAD which directly activate TRPM2 to allow Ca²⁺ influx.
• TRPM3 is a Ca²⁺-permeable, nonselective cation channel. Its activity is increased by hypotonicity.
• TRPM4 and TRPM5 are permeable to monovalent cations but not to Ca²⁺. They are activated by intracellular Ca²⁺. Channel opening is inhibited free ATP, ADP and AMP.
• TRPM6 and TRPM7 both contain a C-terminal protein kinase domain.
• TRPM8 is an outwardly rectifying channel activated by cold and cooling agents, such as menthol and icilin. TRPM8 channels are permeable to Ca²⁺²⁺ in response to cold and menthol. and account for increases in intracellular Ca