Jump to: Page Content, Section Navigation, Site Navigation, Site Search, Account Information, or Site Tools.
|
|
Sci. Signal., 19 May 2009 RESEARCHTRPM2 Functions as a Lysosomal Ca2+-Release Channel in β CellsIngo Lange1,2, Shinichiro Yamamoto3, Santiago Partida-Sanchez4,5, Yasuo Mori3, Andrea Fleig1,2, and Reinhold Penner1,2*
1 Center for Biomedical Research, The Queens Medical Center, Honolulu, HI 96813, USA. Abstract: TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intracellular calcium concentration ([Ca2+]i), but the mechanisms involved are not understood. Using short interfering RNA and a knockout mouse, we report that TRPM2, in addition to its role as a plasma membrane channel, also functions as a Ca2+-release channel activated by intracellular ADPR in a lysosomal compartment. We show that both functions of TRPM2 are critically linked to hydrogen peroxide–induced β cell death. Additionally, extracellular ADPR production by the ectoenzyme CD38 from its substrates NAD+ (nicotinamide adenine dinucleotide) or cADPR causes IP3-dependent Ca2+ release via P2Y and adenosine receptors. Thus, ADPR and TRPM2 represent multimodal signaling elements regulating Ca2+ mobilization in β cells through membrane depolarization, Ca2+ influx, and release of Ca2+ from intracellular stores. * To whom correspondence should be addressed. E-mail: rpenner{at}hawaii.edu
Citation: I. Lange, S. Yamamoto, S. Partida-Sanchez, Y. Mori, A. Fleig, R. Penner, TRPM2 Functions as a Lysosomal Ca2+-Release Channel in β Cells. Sci. Signal. 2, ra23 (2009). The editors suggest the following Related Resources on Science sites:In Science Signaling
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
|
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882