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rdf:type |
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lifeskim:mentions |
umls-concept:C0027270,
umls-concept:C0037083,
umls-concept:C0178539,
umls-concept:C0178719,
umls-concept:C0183210,
umls-concept:C0205314,
umls-concept:C0441712,
umls-concept:C0596235,
umls-concept:C0635005,
umls-concept:C0679622,
umls-concept:C1383501,
umls-concept:C1413221,
umls-concept:C1710082,
umls-concept:C1948027,
umls-concept:C2752529
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pubmed:issue |
3
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pubmed:dateCreated |
2002-3-4
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pubmed:abstractText |
CD38 is an ectocyclase that converts NAD+ to the Ca2+-releasing second messenger cyclic ADP-ribose (cADPr). Here we report that in addition to CD38 ecto-catalysis, intracellularly expressed CD38 may catalyze NAD+-->cADPr conversion to cause cytosolic Ca2+ release. High levels of CD38 were found in the plasma membranes, endoplasmic reticulum, and nuclear membranes of osteoblastic MC3T3-E1 cells. More important, intracellular CD38 was colocalized with target ryanodine receptors. The cyclase also converted a NAD+ surrogate, NGD+, to its fluorescent product, cGDPr (Km approximately 5.13 microM). NAD+ also triggered a cytosolic Ca2+ signal. Similar results were obtained with NIH3T3 cells, which overexpressed a CD38-EGFP fusion protein. The Delta(-49)-CD38-EGFP mutant with a deleted amino-terminal tail and transmembrane domain appeared mainly in the mitochondria with an expected loss of its membrane localization, but the NAD+-induced cytosolic Ca2+ signal was preserved. Likewise, Ca2+ release persisted in cells transfected with the Myr-Delta(-49)-CD38-EGFP or Delta(-49)-CD38-EGFP-Fan mutants, both directed to the plasma membrane but in an opposite topology to the full-length CD38-EGFP. Finally, ryanodine inhibited Ca2+ signaling, indicating the downstream activation of ryanodine receptors by cADPr. We conclude that intracellularly expressed CD38 might link cellular NAD+ production to cytosolic Ca2+ signaling.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP-ribosyl Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD38,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Cd38 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/NAD,
http://linkedlifedata.com/resource/pubmed/chemical/NAD Nucleosidase,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ryanodine Receptor Calcium Release...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1530-6860
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pubmed:author |
pubmed-author:AbeEtsukoE,
pubmed-author:AdebanjoOlugbenga AOA,
pubmed-author:AnandatheerthavaradaHindupur KHK,
pubmed-author:AvadhaniNarayan GNG,
pubmed-author:BevisPeter J RPJ,
pubmed-author:BiswasGopaG,
pubmed-author:EpsteinSolomonS,
pubmed-author:HuangChristopher L-HCL,
pubmed-author:IqbalJameelJ,
pubmed-author:KovalAnatoliyA,
pubmed-author:KumegawaMasoyoshiM,
pubmed-author:MoongaBaljit SBS,
pubmed-author:VioMM,
pubmed-author:WuXing YXY,
pubmed-author:WuXue BXB,
pubmed-author:ZaidiMoneM
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pubmed:issnType |
Electronic
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
302-14
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11874980-3T3 Cells,
pubmed-meshheading:11874980-ADP-ribosyl Cyclase,
pubmed-meshheading:11874980-Animals,
pubmed-meshheading:11874980-Antigens, CD,
pubmed-meshheading:11874980-Antigens, CD38,
pubmed-meshheading:11874980-Antigens, Differentiation,
pubmed-meshheading:11874980-Calcium Signaling,
pubmed-meshheading:11874980-Cell Line,
pubmed-meshheading:11874980-Cell Membrane,
pubmed-meshheading:11874980-Cell Nucleus,
pubmed-meshheading:11874980-Cytosol,
pubmed-meshheading:11874980-Endoplasmic Reticulum,
pubmed-meshheading:11874980-Green Fluorescent Proteins,
pubmed-meshheading:11874980-Indicators and Reagents,
pubmed-meshheading:11874980-Intracellular Membranes,
pubmed-meshheading:11874980-Luminescent Proteins,
pubmed-meshheading:11874980-Membrane Glycoproteins,
pubmed-meshheading:11874980-Mice,
pubmed-meshheading:11874980-Microscopy, Confocal,
pubmed-meshheading:11874980-Models, Biological,
pubmed-meshheading:11874980-Mutation,
pubmed-meshheading:11874980-NAD,
pubmed-meshheading:11874980-NAD+ Nucleosidase,
pubmed-meshheading:11874980-Osteoblasts,
pubmed-meshheading:11874980-Recombinant Fusion Proteins,
pubmed-meshheading:11874980-Ryanodine Receptor Calcium Release Channel
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pubmed:year |
2002
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pubmed:articleTitle |
A novel mechanism for coupling cellular intermediary metabolism to cytosolic Ca2+ signaling via CD38/ADP-ribosyl cyclase, a putative intracellular NAD+ sensor.
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pubmed:affiliation |
Mount Sinai Bone Program, Department of Medicine, and Bronx Veterans Affairs Geriatrics Research Education and Clinical Center (GRECC), New York, New York 10029, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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