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dc.contributor.authorThillaiappan, Nagendra Babuen
dc.contributor.authorSmith, Holly Aen
dc.contributor.authorAtakpa-Adaji, Peaceen
dc.contributor.authorTaylor, Colinen
dc.date.accessioned2021-08-16T23:31:11Z
dc.date.available2021-08-16T23:31:11Z
dc.date.issued2021-07-23en
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/326833
dc.description.abstractRegulation of IP3 receptors (IP3Rs) by IP3 and Ca2+ allows regenerative Ca2+ signals, the smallest being Ca2+ puffs, which arise from coordinated openings of a few clustered IP3Rs. Cells express thousands of mostly mobile IP3Rs, yet Ca2+ puffs occur at a few immobile IP3R clusters. By imaging cells with endogenous IP3Rs tagged with EGFP, we show that KRas-induced actin-interacting protein (KRAP) tethers IP3Rs to actin beneath the plasma membrane. Loss of KRAP abolishes Ca2+ puffs and the global increases in cytosolic Ca2+ concentration evoked by more intense stimulation. Over-expressing KRAP immobilizes additional IP3R clusters and results in more Ca2+ puffs and larger global Ca2+ signals. Endogenous KRAP determines which IP3Rs will respond: it tethers IP3R clusters to actin alongside sites where store-operated Ca2+ entry occurs, licenses IP3Rs to evoke Ca2+ puffs and global cytosolic Ca2+ signals, implicates the actin cytoskeleton in IP3R regulation and may allow local activation of Ca2+ entry.
dc.description.sponsorshipEmmanuel College Cambridge
dc.format.mediumElectronicen
dc.languageengen
dc.publisherNature Research
dc.rightsAll rights reserved
dc.subjectHela Cellsen
dc.subjectCytosolen
dc.subjectAnimalsen
dc.subjectHumansen
dc.subjectCalciumen
dc.subjectMicrofilament Proteinsen
dc.subjectActinsen
dc.subjectMembrane Proteinsen
dc.subjectMicroscopy, Fluorescenceen
dc.subjectRNA Interferenceen
dc.subjectProtein Bindingen
dc.subjectInositol 1,4,5-Trisphosphate Receptorsen
dc.subjectHEK293 Cellsen
dc.titleKRAP tethers IP<sub>3</sub> receptors to actin and licenses them to evoke cytosolic Ca<sup>2+</sup> signals.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2021en
prism.publicationNameNature communicationsen
prism.startingPage4514
prism.volume12en
dc.identifier.doi10.17863/CAM.74281
dcterms.dateAccepted2021-07-01en
rioxxterms.versionofrecord10.1038/s41467-021-24739-9en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2021-07-23en
dc.contributor.orcidThillaiappan, Nagendra Babu [0000-0001-5641-4067]
dc.contributor.orcidTaylor, Colin [0000-0001-7771-1044]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (101844/Z/13/Z)
pubs.funder-project-idBBSRC (BB/T012986/1)


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