Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 19 May 2009
Vol. 2, Issue 71, p. ra23
[DOI: 10.1126/scisignal.2000278]

RESEARCH ARTICLES

Editor's Summary

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.

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).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Small regulators, major consequences - Ca2+ and cholesterol at the endosome-ER interface.
R. van der Kant and J. Neefjes (2014)
J. Cell Sci. 127, 929-938
   Abstract »    Full Text »    PDF »
Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake.
S. Feng, H. Li, Y. Tai, J. Huang, Y. Su, J. Abramowitz, M. X. Zhu, L. Birnbaumer, and Y. Wang (2013)
PNAS 110, 11011-11016
   Abstract »    Full Text »    PDF »
A differential role of macrophage TRPM2 channels in Ca2+ signaling and cell death in early responses to H2O2.
J. Zou, J. F. Ainscough, W. Yang, A. Sedo, S.-P. Yu, Z.-Z. Mei, A. Sivaprasadarao, D. J. Beech, and L.-H. Jiang (2013)
Am J Physiol Cell Physiol 305, C61-C69
   Abstract »    Full Text »    PDF »
Regulation of Ion Channels by Pyridine Nucleotides.
P. J. Kilfoil, S. M. Tipparaju, O. A. Barski, and A. Bhatnagar (2013)
Circ. Res. 112, 721-741
   Abstract »    Full Text »    PDF »
Constitutive lysosome exocytosis releases ATP and engages P2Y receptors in human monocytes.
V. Sivaramakrishnan, S. Bidula, H. Campwala, D. Katikaneni, and S. J. Fountain (2012)
J. Cell Sci. 125, 4567-4575
   Abstract »    Full Text »    PDF »
Cell Death and Autophagy under Oxidative Stress: Roles of Poly(ADP-Ribose) Polymerases and Ca2+.
P. Wyrsch, C. Blenn, J. Bader, and F. R. Althaus (2012)
Mol. Cell. Biol. 32, 3541-3553
   Abstract »    Full Text »    PDF »
A Mechanism of Intracellular P2X Receptor Activation.
V. Sivaramakrishnan and S. J. Fountain (2012)
J. Biol. Chem. 287, 28315-28326
   Abstract »    Full Text »    PDF »
Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents.
B. Toth and L. Csanady (2012)
PNAS 109, 13440-13445
   Abstract »    Full Text »    PDF »
NAD+ Levels Control Ca2+ Store Replenishment and Mitogen-induced Increase of Cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 Channel Gating in Human T Lymphocytes.
M. Magnone, I. Bauer, A. Poggi, E. Mannino, L. Sturla, M. Brini, E. Zocchi, A. De Flora, A. Nencioni, and S. Bruzzone (2012)
J. Biol. Chem. 287, 21067-21081
   Abstract »    Full Text »    PDF »
A TRP that makes us feel hyper.
C. W. Bourque, F. Guilak, and W. Liedtke (2012)
J. Physiol. 590, 1779-1780
   Full Text »    PDF »
TRPM2 Ca2+ channel regulates energy balance and glucose metabolism.
Z. Zhang, W. Zhang, D. Y. Jung, H. J. Ko, Y. Lee, R. H. Friedline, E. Lee, J. Jun, Z. Ma, F. Kim, et al. (2012)
Am J Physiol Endocrinol Metab 302, E807-E816
   Abstract »    Full Text »    PDF »
Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat.
K. K. H. Chung, P. S. Freestone, and J. Lipski (2011)
J Neurophysiol 106, 2865-2875
   Abstract »    Full Text »    PDF »
Waixenicin A Inhibits Cell Proliferation through Magnesium-dependent Block of Transient Receptor Potential Melastatin 7 (TRPM7) Channels.
S. Zierler, G. Yao, Z. Zhang, W. C. Kuo, P. Porzgen, R. Penner, F. D. Horgen, and A. Fleig (2011)
J. Biol. Chem. 286, 39328-39335
   Abstract »    Full Text »    PDF »
Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ release.
A. Sumoza-Toledo, I. Lange, H. Cortado, H. Bhagat, Y. Mori, A. Fleig, R. Penner, and S. Partida-Sanchez (2011)
FASEB J 25, 3529-3542
   Abstract »    Full Text »    PDF »
A Cool Channel in Cold Transduction.
R. Latorre, S. Brauchi, R. Madrid, and P. Orio (2011)
Physiology 26, 273-285
   Abstract »    Full Text »    PDF »
Review: NAD + : A modulator of immune functions.
A. Grahnert, A. Grahnert, C. Klein, E. Schilling, J. Wehrhahn, and S. Hauschildt (2011)
Innate Immunity 17, 212-233
   Abstract »    PDF »
TRPM2: a multifunctional ion channel for calcium signalling.
A. Sumoza-Toledo and R. Penner (2011)
J. Physiol. 589, 1515-1525
   Abstract »    Full Text »    PDF »
Role of TRP Channels in the Regulation of the Endosomal Pathway.
K. Abe and R. Puertollano (2011)
Physiology 26, 14-22
   Abstract »    Full Text »    PDF »
Lack of TRPM2 Impaired Insulin Secretion and Glucose Metabolisms in Mice.
K. Uchida, K. Dezaki, B. Damdindorj, H. Inada, T. Shiuchi, Y. Mori, T. Yada, Y. Minokoshi, and M. Tominaga (2011)
Diabetes 60, 119-126
   Abstract »    Full Text »    PDF »
State-dependent Inhibition of TRPM2 Channel by Acidic pH.
W. Yang, J. Zou, R. Xia, M. L. Vaal, V. A. Seymour, J. Luo, D. J. Beech, and L.-H. Jiang (2010)
J. Biol. Chem. 285, 30411-30418
   Abstract »    Full Text »    PDF »
The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling.
M. Gees, B. Colsoul, and B. Nilius (2010)
Cold Spring Harb Perspect Biol 2, a003962
   Abstract »    Full Text »    PDF »
International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family.
L.-J. Wu, T.-B. Sweet, and D. E. Clapham (2010)
Pharmacol. Rev. 62, 381-404
   Abstract »    Full Text »    PDF »
A Single Residue in a Novel ADP-ribosyl Cyclase Controls Production of the Calcium-mobilizing Messengers Cyclic ADP-ribose and Nicotinic Acid Adenine Dinucleotide Phosphate.
L. Ramakrishnan, H. Muller-Steffner, C. Bosc, V. D. Vacquier, F. Schuber, M.-J. Moutin, L. Dale, and S. Patel (2010)
J. Biol. Chem. 285, 19900-19909
   Abstract »    Full Text »    PDF »
The calcium-permeable non-selective cation channel TRPM2 is modulated by cellular acidification.
J. G. Starkus, A. Fleig, and R. Penner (2010)
J. Physiol. 588, 1227-1240
   Abstract »    Full Text »    PDF »
Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice.
B. Colsoul, A. Schraenen, K. Lemaire, R. Quintens, L. Van Lommel, A. Segal, G. Owsianik, K. Talavera, T. Voets, R. F. Margolskee, et al. (2010)
PNAS 107, 5208-5213
   Abstract »    Full Text »    PDF »
Calcium signaling via two-pore channels: local or global, that is the question.
M. X. Zhu, J. Ma, J. Parrington, P. J. Calcraft, A. Galione, and A. M. Evans (2010)
Am J Physiol Cell Physiol 298, C430-C441
   Abstract »    Full Text »    PDF »
In with the TRP Channels: Intracellular Functions for TRPM1 and TRPM2.
S. Patel and R. Docampo (2009)
Science Signaling 2, pe69
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882