KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals.
dc.contributor.author | Thillaiappan, Nagendra Babu | |
dc.contributor.author | Smith, Holly A | |
dc.contributor.author | Atakpa-Adaji, Peace | |
dc.contributor.author | Taylor, Colin W | |
dc.date.accessioned | 2021-08-16T23:31:11Z | |
dc.date.available | 2021-08-16T23:31:11Z | |
dc.date.issued | 2021-07-23 | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://www.repository.cam.ac.uk/handle/1810/326833 | |
dc.description.abstract | Regulation 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.sponsorship | Emmanuel College Cambridge | |
dc.format.medium | Electronic | |
dc.language | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.rights | All rights reserved | |
dc.subject | Hela Cells | |
dc.subject | Cytosol | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Calcium | |
dc.subject | Microfilament Proteins | |
dc.subject | Actins | |
dc.subject | Membrane Proteins | |
dc.subject | Microscopy, Fluorescence | |
dc.subject | RNA Interference | |
dc.subject | Protein Binding | |
dc.subject | Inositol 1,4,5-Trisphosphate Receptors | |
dc.subject | HEK293 Cells | |
dc.title | KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals. | |
dc.type | Article | |
prism.issueIdentifier | 1 | |
prism.publicationDate | 2021 | |
prism.publicationName | Nat Commun | |
prism.startingPage | 4514 | |
prism.volume | 12 | |
dc.identifier.doi | 10.17863/CAM.74281 | |
dcterms.dateAccepted | 2021-07-01 | |
rioxxterms.versionofrecord | 10.1038/s41467-021-24739-9 | |
rioxxterms.version | AM | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2021-07-23 | |
dc.contributor.orcid | Thillaiappan, Nagendra Babu [0000-0001-5641-4067] | |
dc.contributor.orcid | Taylor, Colin W [0000-0001-7771-1044] | |
dc.identifier.eissn | 2041-1723 | |
rioxxterms.type | Journal Article/Review | |
pubs.funder-project-id | Wellcome Trust (101844/Z/13/Z) | |
pubs.funder-project-id | BBSRC (BB/T012986/1) | |
cam.issuedOnline | 2021-07-23 |
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