Blog
About

98
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      NAADP mobilizes calcium from acidic organelles through two-pore channels

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Ca 2+ mobilization from intracellular stores represents an important cell signaling process 1 which is regulated, in mammalian cells, by inositol 1,4,5-trisphosphate (InsP 3), cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). InsP 3 and cADPR release Ca 2+ from sarco / endoplasmic reticulum (S/ER) stores through activation of InsP 3 and ryanodine receptors (InsP 3Rs and RyRs). By contrast, the nature of the intracellular stores targeted by NAADP and molecular identity of the NAADP receptors remain controversial 1, 2, although evidence indicates that NAADP mobilizes Ca 2+ from lysosome-related acidic compartments 3, 4. Here we show that two-pore channels (TPCs) comprise a family of NAADP receptors, with TPC1 and TPC3 being expressed on endosomal and TPC2 on lysosomal membranes. Membranes enriched with TPC2 exhibit high affinity NAADP binding and TPC2 underpins NAADP-induced Ca 2+ release from lysosome-related stores that is subsequently amplified by Ca 2+-induced Ca 2+ release via InsP 3Rs. Responses to NAADP were abolished by disrupting the lysosomal proton gradient and by ablating TPC2 expression, but only attenuated by depleting ER Ca 2+ stores or blocking InsP 3Rs. Thus, TPCs form NAADP receptors that release Ca 2+ from acidic organelles, which can trigger additional Ca 2+ signals via S/ER. TPCs therefore provide new insights into the regulation and organization of Ca 2+ signals in animal cells and will advance our understanding of the physiological role of NAADP.

          Related collections

          Most cited references 30

          • Record: found
          • Abstract: not found
          • Article: not found

          Calcium signalling: dynamics, homeostasis and remodelling.

          Ca2+ is a highly versatile intracellular signal that operates over a wide temporal range to regulate many different cellular processes. An extensive Ca2+-signalling toolkit is used to assemble signalling systems with very different spatial and temporal dynamics. Rapid highly localized Ca2+ spikes regulate fast responses, whereas slower responses are controlled by repetitive global Ca2+ transients or intracellular Ca2+ waves. Ca2+ has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The vacuolar Ca2+-activated channel TPC1 regulates germination and stomatal movement.

            Cytosolic free calcium ([Ca2+]cyt) is a ubiquitous signalling component in plant cells. Numerous stimuli trigger sustained or transient elevations of [Ca2+]cyt that evoke downstream stimulus-specific responses. Generation of [Ca2+]cyt signals is effected through stimulus-induced opening of Ca2+-permeable ion channels that catalyse a flux of Ca2+ into the cytosol from extracellular or intracellular stores. Many classes of Ca2+ current have been characterized electrophysiologically in plant membranes. However, the identity of the ion channels that underlie these currents has until now remained obscure. Here we show that the TPC1 ('two-pore channel 1') gene of Arabidopsis thaliana encodes a class of Ca2+-dependent Ca2+-release channel that is known from numerous electrophysiological studies as the slow vacuolar channel. Slow vacuolar channels are ubiquitous in plant vacuoles, where they form the dominant conductance at micromolar [Ca2+]cyt. We show that a tpc1 knockout mutant lacks functional slow vacuolar channel activity and is defective in both abscisic acid-induced repression of germination and in the response of stomata to extracellular calcium. These studies unequivocally demonstrate a critical role of intracellular Ca2+-release channels in the physiological processes of plants.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs.

              Nicotinic acid adenine dinucleotide phosphate (NAADP) mobilizes Ca(2+) in many cells and species. Unlike other Ca(2+)-mobilizing messengers, NAADP mobilizes Ca(2+) from an unknown store that is not the endoplasmic reticulum, the store traditionally associated with messenger-mediated Ca(2+) signaling. Here, we demonstrate the presence of a Ca(2+) store in sea urchin eggs mobilized by NAADP that is dependent on a proton gradient maintained by an ATP-dependent vacuolar-type proton pump. Moreover, we provide pharmacological and biochemical evidence that this Ca(2+) store is the reserve granule, the functional equivalent of a lysosome in the sea urchin egg. These findings represent an unsuspected mechanism for messenger-mediated Ca(2+) release from lysosome-related organelles.
                Bookmark

                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                0028-0836
                1476-4687
                6 April 2009
                22 April 2009
                28 May 2009
                28 November 2009
                : 459
                : 7246
                : 596-600
                Affiliations
                [1 ]Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland UK
                [2 ]Department of Pharmacology, University of Oxford, Oxford, UK
                [3 ]Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA
                [4 ]College of Life Sciences, Peking University, Beijing, China
                [5 ]Department of Neuroscience and Center for Molecular Neurobiology, The Ohio State University, Columbus, OH, USA
                [6 ]MRC Harwell, Oxfordshire, UK
                Author notes
                [*]

                Address correspondence to: Dr. Michael X. Zhu, Center for Molecular Neurobiology, The Ohio State University, 168 Rightmire Hall, 1060 Carmack Road, Columbus, OH 43210, USA. Tel: (614)292-8173, Fax: (614)292-5379, email: zhu.55@ 123456osu.edu

                [¶]

                Equal contributing authors

                Article
                nihpa107904
                10.1038/nature08030
                2761823
                19387438
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: R21 NS056942-01 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: R01 NS042183-04 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: R01 DK081654-01A1 ||DK
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P30 NS045758-059003 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P30 NS045758-05 ||NS
                Categories
                Article

                Uncategorized

                Comments

                Comment on this article