ArticleThe Journal of biological chemistry2011
Connexin-43 hemichannels mediate cyclic ADP-ribose generation and its Ca2+-mobilizing activity by NAD+/cyclic ADP-ribose transport.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- HIV heart inflammation is mediated by HIV infected myeloid cells, HIV-tat secretion, and aberrant function of Connexin43-containing channels.Scientific reports · 2026Article
- NADNature metabolism · 2025Review
- Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP)-Mediated Calcium Signaling Is Active in Memory CD4Molecules (Basel, Switzerland) · 2024Article
- Evolving roles of CD38 metabolism in solid tumour microenvironment.British journal of cancer · 2023Review
- Review
- Novel Approaches Used to Examine and Control Neurogenesis in Parkinson's Disease.International journal of molecular sciences · 2021Review
- Role of PGC-1α in the Mitochondrial NADInternational journal of molecular sciences · 2021Review
- Sex-related differences in human plasma NAD+/NADH levels depend on age.Bioscience reports · 2021Article
- Need for NADCells · 2020Review
- HIV Disease Progression: Overexpression of the Ectoenzyme CD38 as a Contributory Factor?BioEssays : news and reviews in molecular, cellular and developmental biology · 2019Review
- Roles of Nmnat1 in the survival of retinal progenitors through the regulation of pro-apoptotic gene expression via histone acetylation.Cell death & disease · 2018Article
- Emerging potential benefits of modulating NADAmerican journal of physiology. Heart and circulatory physiology · 2018Review
- CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms.Mediators of inflammation · 2018Review
- Physiology of Astroglia.Physiological reviews · 2018Review
- cAMP-dependent recruitment of acidic organelles for Ca2+ signaling in the salivary gland.American journal of physiology. Cell physiology · 2016Article
- Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.The Journal of biological chemistry · 2016Article
- Connexins and Pannexins: New Insights into Microglial Functions and Dysfunctions.Frontiers in molecular neuroscience · 2016Review
- Role of Astroglial Hemichannels and Pannexons in Memory and Neurodegenerative Diseases.Frontiers in integrative neuroscience · 2016Review
- Article
- The human NAD metabolome: Functions, metabolism and compartmentalization.Critical reviews in biochemistry and molecular biology · 2015Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ADP-ribosyl cyclase CD38 whose catalytic domain resides in outside of the cell surface produces the second messenger cyclic ADP-ribose (cADPR) from NAD(+). cADPR increases intracellular Ca(2+) through the intracellular ryanodine receptor/Ca(2+) release channel (RyR). It has been known that intracellular NAD(+) approaches ecto-CD38 via its export by connexin (Cx43) hemichannels, a component of gap junctions. However, it is unclear how cADPR extracellularly generated by ecto-CD38 approaches intracellular RyR although CD38 itself or nucleoside transporter has been proposed to import cADPR. Moreover, it has been unknown what physiological stimulation can trigger Cx43-mediated export of NAD(+). Here we demonstrate that Cx43 hemichannels, but not CD38, import cADPR to increase intracellular calcium through RyR. We also demonstrate that physiological stimulation such as Fcγ receptor (FcγR) ligation induces calcium mobilization through three sequential steps, Cx43-mediated NAD(+) export, CD38-mediated generation of cADPR and Cx43-mediated cADPR import in J774 cells. Protein kinase A (PKA) activation also induced calcium mobilization in the same way as FcγR stimulation. FcγR stimulation-induced calcium mobilization was blocked by PKA inhibition, indicating that PKA is a linker between FcγR stimulation and NAD(+)/cADPR transport. Cx43 knockdown blocked extracellular cADPR import and extracellular cADPR-induced calcium mobilization in J774 cells. Cx43 overexpression in Cx43-negative cells conferred extracellular cADPR-induced calcium mobilization by the mediation of cADPR import. Our data suggest that Cx43 has a dual function exporting NAD(+) and importing cADPR into the cell to activate intracellular calcium mobilization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.