Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response.
In just a few years, the discovery and subsequent characterization of several members of the TRPM family of cation channels have provided us with surprising new insights into unknown aspects of cellular ion-homeostasis regulation. This includes reports about ADP-ribose functioning as a novel intracellular second messenger and gating molecule of the Ca(2+)-permeable TRPM2 channel, studies demonstrating the central role of mouse TRPM5 in taste signaling, as well as the unexpected involvement of TRPM6 and TRPM7 in regulating Mg(2+)-homeostasis, or the cool properties of TRPM8 acting as a cold and menthol sensor in sensory neurons. At least four of the eight known TRPM proteins have been shown to be present in the immune context: TRPM1 (melastatin), TRPM2, TRPM4 and TRPM7. Although we currently lack animal models allowing a detailed assessment of the potential involvement of TRPM family members in modulating the immune response, the powerful combination of molecular and cellular biology, biochemistry, and electrophysiology have provided the first clues as to how these molecules could contribute to immunity.
Perraud
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AL
Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206, USA. perrauda@njc.org
Knowles
H M
HM
Schmitz
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D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000276:immunology / Q000502:physiology; D027682:Cation Transport Proteins / Q000276:immunology / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D008274:Magnesium / Q000502:physiology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology; D011494:Protein Kinases / Q000276:immunology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D050053:TRPM Cation Channels
D015220:Calcium Channels; D027682:Cation Transport Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; C437888:TRPM4 protein, human; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D008274:Magnesium; D002118:Calcium