Premium
TRPM2 activation by cyclic ADP‐ribose at body temperature is involved in insulin secretion
Author(s) -
Togashi Kazuya,
Hara Yuji,
Tominaga Tomoko,
Higashi Tomohiro,
Konishi Yasunobu,
Mori Yasuo,
Tominaga Makoto
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601083
Subject(s) - trpm2 , transient receptor potential channel , biology , cytosol , insulinoma , cyclic adp ribose , insulin , intracellular , nad+ kinase , pancreatic islets , secretion , microbiology and biotechnology , biochemistry , biophysics , endocrinology , islet , receptor , enzyme , cd38 , stem cell , cd34
There are eight thermosensitive TRP (transient receptor potential) channels in mammals, and there might be other TRP channels sensitive to temperature stimuli. Here, we demonstrate that TRPM2 can be activated by exposure to warm temperatures (>35°C) apparently via direct heat‐evoked channel gating. β‐NAD + ‐ or ADP‐ribose‐evoked TRPM2 activity is robustly potentiated at elevated temperatures. We also show that, even though cyclic ADP‐ribose (cADPR) does not activate TRPM2 at 25°C, co‐application of heat and intracellular cADPR dramatically potentiates TRPM2 activity. Heat and cADPR evoke similar responses in rat insulinoma RIN‐5F cells, which express TRPM2 endogenously. In pancreatic islets, TRPM2 is coexpressed with insulin, and mild heating of these cells evokes increases in both cytosolic Ca 2+ and insulin release, which is K ATP channel‐independent and protein kinase A‐mediated. Heat‐evoked responses in both RIN‐5F cells and pancreatic islets are significantly diminished by treatment with TRPM2‐specific siRNA. These results identify TRPM2 as a potential molecular target for cADPR, and suggest that TRPM2 regulates Ca 2+ entry into pancreatic β‐cells at body temperature depending on the production of cADPR‐related molecules, thereby regulating insulin secretion.