Research ArticleIon Channels

TRPM2 Functions as a Lysosomal Ca2+-Release Channel in β Cells

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Science Signaling  19 May 2009:
Vol. 2, Issue 71, pp. ra23
DOI: 10.1126/scisignal.2000278

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Coordinating Calcium Signals

TRPM2 (transient receptor potential channel, melastatin subfamily type 2) is a Ca2+-permeable ion channel found in the plasma membrane, whose activation by adenosine diphosphoribose and other adenine dinucleotides can lead to apoptosis. Lange et al. now show that TRPM2 is present in lysosomes, where it can be activated by adenosine diphosphoribose to release Ca2+ from internal stores. Moreover, both plasma membrane and lysosomal TRPM2 played crucial roles in mediating pancreatic β cell death in response to peroxide, a process thought to be involved in the development of diabetes. Although adenosine diphosphoribose acts intracellularly to activate both pools of TRPM2, the authors found that it also acts extracellularly through two classes of G protein–coupled receptors to elicit Ca2+ release from intracellular stores through a distinct pathway that was independent of TRPM2. Thus, both TRPM2 and adenosine diphosphoribose play dual roles in increasing cytoplasmic Ca2+ in pancreatic β cells.

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