Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)
Abstract
Cyclic ADP-ribose (cADPR) is a Ca2+ mobilizing second messenger found in various cell types, tissues and organisms. Receptor-mediated formation of cADPR may proceed via transmembrane shuttling of the substrate NAD and involvement of the ectoenzyme CD38, or via so far unidentified ADP-ribosyl cyclases located within the cytosol or in internal membranes. cADPR activates intracellular Ca2+ release via type 2 and 3 ryanodine receptors. The exact molecular mechanism, however, remains to be elucidated. Possibilities are the direct binding of cADPR to the ryanodine receptor or binding via a separate cADPR binding protein. In addition to Ca2+ release, cADPR also evokes Ca2+ entry. The underlying mechanism(s) may comprise activation of capacitative Ca2+ entry and/or activation of the cation channel TRPM2 in conjunction with adenosine diphosphoribose. The development of novel cADPR analogues revealed new insights into the structure-activity relationship. Substitution of either the northern ribose or both the northern and southern ribose resulted in much simpler molecules, which still retained significant biological activity.
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CD38 is expressed in the brain and can catalyze the formation of cADPR from NAD+.
“CD38 is expressed in the brain (Lee, 2001;Higashida et al., 2007) and can catalyze the formation of cyclic ADP-ribose (cADPR) from NAD + (Lee, 2001;Guse, 2005;Malvasi et al., 2008).”
From Two genetic variants of CD38 in subjects with autism spectrum disorder and controls (2010) · cites this paper as Guse, 2005
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- Authors
- Guse, A. H.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Guse, Andreas H.
- ORCID
- Guse, Andreas H.
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2005-08-26
- Volume
- 272
- Issue
- 18
- Pages
- 4590-4597
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W1969246107
- Cited by
- 139
- References
- 64
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 6 · 2012: 7
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- cyclic ADP-ribose, second messengers, calcium mobilization, ryanodine receptor, CD38, ADP-ribosyl cyclase, NAD+, structure-activity relationship, TRPM2, store-operated calcium entry, intracellular calcium release, cation channels
- MeSH terms
- Animals, Calcium, Glycoproteins, Humans, Structure-Activity Relationship, Second Messenger Systems, Molecular Chaperones, Ryanodine Receptor Calcium Release Channel, Calcium Signaling, Cyclic ADP-Ribose, Clusterin
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