Cited by 140Calcium signaling and nucleotide metabolismAdenosine and Purinergic SignalingBiochemical and Molecular Research

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Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)

Guse, Andreas H.·2005·The FEBS Journal

DOI 10.1111/j.1742-4658.2005.04863.x

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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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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
DOI: 10.1111/j.1742-4658.2005.04863.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Second messenger function and the structure–activity relationship of cyclic adenosine diphosphoribose (cADPR)

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