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dc.contributor.authorThillaiappan, Nagendra Babu
dc.contributor.authorSmith, Holly A
dc.contributor.authorAtakpa-Adaji, Peace
dc.contributor.authorTaylor, Colin W
dc.date.accessioned2021-08-16T23:31:11Z
dc.date.available2021-08-16T23:31:11Z
dc.date.issued2021-07-23
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.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAll rights reserved
dc.subjectHela Cells
dc.subjectCytosol
dc.subjectAnimals
dc.subjectHumans
dc.subjectCalcium
dc.subjectMicrofilament Proteins
dc.subjectActins
dc.subjectMembrane Proteins
dc.subjectMicroscopy, Fluorescence
dc.subjectRNA Interference
dc.subjectProtein Binding
dc.subjectInositol 1,4,5-Trisphosphate Receptors
dc.subjectHEK293 Cells
dc.titleKRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2021
prism.publicationNameNat Commun
prism.startingPage4514
prism.volume12
dc.identifier.doi10.17863/CAM.74281
dcterms.dateAccepted2021-07-01
rioxxterms.versionofrecord10.1038/s41467-021-24739-9
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-07-23
dc.contributor.orcidThillaiappan, Nagendra Babu [0000-0001-5641-4067]
dc.contributor.orcidTaylor, Colin W [0000-0001-7771-1044]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (101844/Z/13/Z)
pubs.funder-project-idBBSRC (BB/T012986/1)
cam.issuedOnline2021-07-23


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