File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Ca2+ Signaling Occurs via Second Messenger Release from Intraorganelle Synthesis Sites

TitleCa2+ Signaling Occurs via Second Messenger Release from Intraorganelle Synthesis Sites
Authors
KeywordsSIGNALING
Issue Date2008
PublisherCell Press. The Journal's web site is located at http://www.current-biology.com/
Citation
Current Biology, 2008, v. 18 n. 20, p. 1612-1618 How to Cite?
AbstractCyclic ADP-ribose is an important Ca2+-mobilizing cytosolic messenger synthesized from β-NAD+ by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response to stimuli. We have cloned and characterized three ARCs in the sea urchin egg and found that endogenous ARCβ and ARCγ are intracellular and located within the lumen of acidic, exocytotic vesicles, where they are optimally active. Intraorganelle ARCs are shielded from cytosolic substrate and targets by the organelle membrane, but this barrier is circumvented by nucleotide transport. We show that a β-NAD+ transporter provides ARC substrate that is converted luminally to cADPR, which, in turn, is shuttled out to the cytosol via a separate cADPR transporter. Moreover, nucleotide transport is integral to ARC activity physiologically because three transport inhibitors all inhibited the fertilization-induced Ca2+ wave that is dependent upon cADPR. This represents a novel signaling mechanism whereby an extracellular stimulus increases the concentration of a second messenger by promoting messenger transport from intraorganelle synthesis sites to the cytosol. © 2008 Elsevier Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/132552
ISSN
2015 Impact Factor: 8.983
2015 SCImago Journal Rankings: 4.729
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Wellcome Trust UK
Medical Research Council, UK
Funding Information:

We thank Clive Garnham for technical assistance. This work was supported by The Wellcome Trust UK (Senior Fellowship to A.G. and a Project Grant to A.G. and J.P.) and Medical Research Council, UK (studentship to L.C.D.).

References

 

DC FieldValueLanguage
dc.contributor.authorDavis, LCen_HK
dc.contributor.authorMorgan, AJen_HK
dc.contributor.authorRuas, Men_HK
dc.contributor.authorWong, JLen_HK
dc.contributor.authorGraeff, RMen_HK
dc.contributor.authorPoustka, AJen_HK
dc.contributor.authorLee, HCen_HK
dc.contributor.authorWessel, GMen_HK
dc.contributor.authorParrington, Jen_HK
dc.contributor.authorGalione, Aen_HK
dc.date.accessioned2011-03-28T09:26:14Z-
dc.date.available2011-03-28T09:26:14Z-
dc.date.issued2008en_HK
dc.identifier.citationCurrent Biology, 2008, v. 18 n. 20, p. 1612-1618en_HK
dc.identifier.issn0960-9822en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132552-
dc.description.abstractCyclic ADP-ribose is an important Ca2+-mobilizing cytosolic messenger synthesized from β-NAD+ by ADP-ribosyl cyclases (ARCs). However, the focus upon ectocellular mammalian ARCs (CD38 and CD157) has led to confusion as to how extracellular enzymes generate intracellular messengers in response to stimuli. We have cloned and characterized three ARCs in the sea urchin egg and found that endogenous ARCβ and ARCγ are intracellular and located within the lumen of acidic, exocytotic vesicles, where they are optimally active. Intraorganelle ARCs are shielded from cytosolic substrate and targets by the organelle membrane, but this barrier is circumvented by nucleotide transport. We show that a β-NAD+ transporter provides ARC substrate that is converted luminally to cADPR, which, in turn, is shuttled out to the cytosol via a separate cADPR transporter. Moreover, nucleotide transport is integral to ARC activity physiologically because three transport inhibitors all inhibited the fertilization-induced Ca2+ wave that is dependent upon cADPR. This represents a novel signaling mechanism whereby an extracellular stimulus increases the concentration of a second messenger by promoting messenger transport from intraorganelle synthesis sites to the cytosol. © 2008 Elsevier Ltd. All rights reserved.en_HK
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.current-biology.com/en_HK
dc.relation.ispartofCurrent Biologyen_HK
dc.subjectSIGNALINGen_HK
dc.titleCa2+ Signaling Occurs via Second Messenger Release from Intraorganelle Synthesis Sitesen_HK
dc.typeArticleen_HK
dc.identifier.emailGraeff, RM: graeffr@hku.hken_HK
dc.identifier.emailLee, HC: leehc@hku.hken_HK
dc.identifier.authorityGraeff, RM=rp01464en_HK
dc.identifier.authorityLee, HC=rp00545en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.cub.2008.09.024en_HK
dc.identifier.pmid18951023-
dc.identifier.pmcidPMC2581485-
dc.identifier.scopuseid_2-s2.0-54149104220en_HK
dc.identifier.hkuros154344-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-54149104220&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue20en_HK
dc.identifier.spage1612en_HK
dc.identifier.epage1618en_HK
dc.identifier.eissn1879-0445-
dc.identifier.isiWOS:000260551400034-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridDavis, LC=19638725100en_HK
dc.identifier.scopusauthoridMorgan, AJ=7403139899en_HK
dc.identifier.scopusauthoridRuas, M=6701317815en_HK
dc.identifier.scopusauthoridWong, JL=9942972700en_HK
dc.identifier.scopusauthoridGraeff, RM=7003614053en_HK
dc.identifier.scopusauthoridPoustka, AJ=35379011300en_HK
dc.identifier.scopusauthoridLee, HC=26642959100en_HK
dc.identifier.scopusauthoridWessel, GM=7004765118en_HK
dc.identifier.scopusauthoridParrington, J=7003274901en_HK
dc.identifier.scopusauthoridGalione, A=7006334937en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats