Immunocyte Ca2+ influx system mediated by LTRPC2.
We characterized an activation mechanism of the human LTRPC2 protein, a member of the transient receptor potential family of ion channels, and demonstrated that LTRPC2 mediates Ca2+ influx into immunocytes. Intracellular pyrimidine nucleotides, adenosine 5'-diphosphoribose (ADPR), and nicotinamide adenine dinucleotide (NAD), directly activated LTRPC2, which functioned as a Ca2+-permeable nonselective cation channel and enabled Ca2+ influx into cells. This activation was suppressed by intracellular adenosine triphosphate. These results reveal that ADPR and NAD act as intracellular messengers and may have an important role in Ca2+ influx by activating LTRPC2 in immunocytes.
Sano
Y
Y
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. sano.yorikata@yamanouchi.co.jp
Inamura
K
K
Miyake
A
A
Mochizuki
S
S
Yokoi
H
H
Matsushime
H
H
Furuichi
K
K
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002460:Cell Line; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels; D019169:Jurkat Cells; D008562:Membrane Glycoproteins; D008564:Membrane Potentials; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D009243:NAD / Q000378:metabolism / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D050053:TRPM Cation Channels
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015220:Calcium Channels; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium