File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Sensitization of calcium-induced calcium release by cyclic ADP-ribose and calmodulin

TitleSensitization of calcium-induced calcium release by cyclic ADP-ribose and calmodulin
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date1995
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1995, v. 270 n. 16, p. 9060-9066 How to Cite?
AbstractCyclic ADP-ribose (cADPR) is emerging as an endogenous regulator of Ca2+-induced Ca2+ release (CICR), and we have recently demonstrated that its action is mediated by calmodulin (CAM) (Lee, H. C., Aarhus, R., Graeff, R., Gurnack, M. E., and Walseth, T. F. (1994) Nature 370, 307-309). In this study we show by immunoblot analyses that the protein factor in sea urchin eggs responsible for conferring cADPR sensitivity to egg microsomes was CaM. This was further supported by the fact that bovine CaM was equally effective as the egg factor. In contrast, plant CaM was only partially active even at 10-20-fold higher concentrations. This exquisite specificity was also shown by binding studies using 125I-labeled bovine CaM. The effectiveness of various CaMs (bovine > spinach > wheat gem) in competing for the binding sites was identical to their potency in conferring cADPR sensitivity to the microsomes. A comparison between bovine and wheat gem CaM in competing for the sites suggests only 10-14% of the total binding was crucial for the activity. Depending on the CaM concentration, the sensitivity of the microsomes to cADPR could be changed by several orders of magnitude. The requirement for CaM could be alleviated by raising the divalent cation concentration with Sr2+. Results showed that CaM, cADPR, and caffeine all act synergistically to increase the divalent cation sensitivity of the CICR mechanism. The combined action of any of the three agonists was sufficient to sensitize the mechanism so much that even the nanomolar concentration of ambient Ca2+ was enough to activate the release. Unlike the CICR mechanism, the microsomal inositol 1,4,5-trisphosphate-sensitive Ca2+ release showed no dependence on CaM. Using an antagonist of CaM, W7, it was demonstrated that the cADPR- but not the inositol 1,4,5-trisphosphate-dependent release mechanism could be blocked in live sea urchin eggs. These results indicate cADPR can function as a physiological modulator of CICR and, together with CaM, can alter the sensitivity of the release mechanism to divalent cation by several orders of magnitude.
Persistent Identifierhttp://hdl.handle.net/10722/132583
ISSN
2020 Impact Factor: 5.157
2023 SCImago Journal Rankings: 1.766
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHon Cheung Leeen_HK
dc.contributor.authorAarhus, Ren_HK
dc.contributor.authorGraeff, RMen_HK
dc.date.accessioned2011-03-28T09:26:31Z-
dc.date.available2011-03-28T09:26:31Z-
dc.date.issued1995en_HK
dc.identifier.citationJournal Of Biological Chemistry, 1995, v. 270 n. 16, p. 9060-9066en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132583-
dc.description.abstractCyclic ADP-ribose (cADPR) is emerging as an endogenous regulator of Ca2+-induced Ca2+ release (CICR), and we have recently demonstrated that its action is mediated by calmodulin (CAM) (Lee, H. C., Aarhus, R., Graeff, R., Gurnack, M. E., and Walseth, T. F. (1994) Nature 370, 307-309). In this study we show by immunoblot analyses that the protein factor in sea urchin eggs responsible for conferring cADPR sensitivity to egg microsomes was CaM. This was further supported by the fact that bovine CaM was equally effective as the egg factor. In contrast, plant CaM was only partially active even at 10-20-fold higher concentrations. This exquisite specificity was also shown by binding studies using 125I-labeled bovine CaM. The effectiveness of various CaMs (bovine > spinach > wheat gem) in competing for the binding sites was identical to their potency in conferring cADPR sensitivity to the microsomes. A comparison between bovine and wheat gem CaM in competing for the sites suggests only 10-14% of the total binding was crucial for the activity. Depending on the CaM concentration, the sensitivity of the microsomes to cADPR could be changed by several orders of magnitude. The requirement for CaM could be alleviated by raising the divalent cation concentration with Sr2+. Results showed that CaM, cADPR, and caffeine all act synergistically to increase the divalent cation sensitivity of the CICR mechanism. The combined action of any of the three agonists was sufficient to sensitize the mechanism so much that even the nanomolar concentration of ambient Ca2+ was enough to activate the release. Unlike the CICR mechanism, the microsomal inositol 1,4,5-trisphosphate-sensitive Ca2+ release showed no dependence on CaM. Using an antagonist of CaM, W7, it was demonstrated that the cADPR- but not the inositol 1,4,5-trisphosphate-dependent release mechanism could be blocked in live sea urchin eggs. These results indicate cADPR can function as a physiological modulator of CICR and, together with CaM, can alter the sensitivity of the release mechanism to divalent cation by several orders of magnitude.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleSensitization of calcium-induced calcium release by cyclic ADP-ribose and calmodulinen_HK
dc.typeArticleen_HK
dc.identifier.emailHon Cheung Lee: leehc@hku.hken_HK
dc.identifier.emailGraeff, RM: graeffr@hku.hken_HK
dc.identifier.authorityHon Cheung Lee=rp00545en_HK
dc.identifier.authorityGraeff, RM=rp01464en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.270.16.9060en_HK
dc.identifier.pmid7721819-
dc.identifier.scopuseid_2-s2.0-0028961777en_HK
dc.identifier.volume270en_HK
dc.identifier.issue16en_HK
dc.identifier.spage9060en_HK
dc.identifier.epage9066en_HK
dc.identifier.isiWOS:A1995QU08900007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHon Cheung Lee=26642959100en_HK
dc.identifier.scopusauthoridAarhus, R=6701339421en_HK
dc.identifier.scopusauthoridGraeff, RM=7003614053en_HK
dc.identifier.issnl0021-9258-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats