cADPR stimulates SERCA activity in Xenopus oocytes |
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| Authors: | Michiko Yamasaki-Mann Angelo Demuro Ian Parker |
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| Institution: | 1. Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, United States;2. Department of Physiology & Biophysics, University of California, Irvine, CA 92697, United States;1. Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, USA;2. Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina;1. Autonomic and Neuroendocrinological Laboratory, Dept. of Neurology, University Hospital Carl Gustav Carus, Dresden Fetscherstr. 74, 01307 Dresden, Germany;2. Research Group Neuro-Metabolism, Dept. of Neurology and Internal Medicine III, University Hospital Carl Gustav Carus, Dresden Fetscherstr. 74, 01307 Dresden, Germany;3. Lipoprotein Apheresis Center, Dept. of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden Fetscherstr. 74, 01307 Dresden, Germany;1. Neurosurgery Department, Regional Specialist Hospital, Olsztyn, Poland;2. Neurosurgery Department, Medical University of Gdańsk, Gdańsk, Poland;3. Department of Molecular Pathology and Neuropathology, Medical University of ?ód?, Poland;4. Department of Preventive Medicine and Education, Medical University of Gdańsk, Gdańsk, Poland;5. Neurosurgery and CNS Oncology Department, Medical University of ?ód?, Poland;1. University of Belgrade, Department of Neurobiology, Institute for Biological Research – Sinisa Stankovic, 11 060 Belgrade, Serbia;2. University of Belgrade, Department for Life Sciences, Institute for Multidisciplinary Research, 11 030 Belgrade, Serbia;1. Centre for Ophthalmology and Visual Science, Lions Eye Institute, The University of Western Australia, Perth, Australia;2. Singapore Eye Research Institute, National University of Singapore, Singapore;1. INSTITUTE OF CANCER RESEARCH AND ROYAL MARSDEN HOSPITAL |
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| Abstract: | The intracellular second messenger cyclic ADP-ribose (cADPR) induces Ca2+ release through the activation of ryanodine receptors (RyRs). Moreover, it has been suggested that cADPR may serve an additional role to modulate sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump activity, but studies have been complicated by concurrent actions on RyR. Here, we explore the actions of cADPR in Xenopus oocytes, which lack RyRs. We examined the effects of cADPR on the sequestration of cytosolic Ca2+ following Ca2+ transients evoked by photoreleased inositol 1,4,5-trisphosphate (InsP3), and by Ca2+ influx through expressed nicotinic acetylcholine receptors (nAChR) in the oocytes membrane. In both cases the decay of the Ca2+ transients was accelerated by intracellular injection of a non-metabolizable analogue of cADPR, 3-Deaza-cADPR, and photorelease of cADPR from a caged precursor demonstrated that this action is rapid (a few s). The acceleration was abolished by pre-treatment with thapsigargin to block SERCA activity, and was inhibited by two specific antagonists of cADPR, 8-NH2-cADPR and 8-br-cADPR. We conclude that cADPR serves to modulate Ca2+ sequestration by enhancing SERCA pump activity, in addition to its well-established action on RyRs to liberate Ca2+. |
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