Repository logo
 

IP3 Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca2+ to Lysosomes.

Simple item page
cam.issuedOnline2018-12-11
dc.contributor.authorAtakpa, Peace
dc.contributor.authorThillaiappan, Nagendra Babu
dc.contributor.authorMataragka, Stefania
dc.contributor.authorProle, David L
dc.contributor.authorTaylor, Colin W
dc.contributor.orcidThillaiappan, Nagendra [0000-0001-5641-4067]
dc.contributor.orcidTaylor, Colin [0000-0001-7771-1044]
dc.date.accessioned2018-12-22T00:31:15Z
dc.date.available2018-12-22T00:31:15Z
dc.date.issued2018-12-11
dc.description.abstractInositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) allow extracellular stimuli to redistribute Ca2+ from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H+-ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca2+ released by all IP3R subtypes, but not Ca2+ entering cells through store-operated Ca2+ entry (SOCE). A low-affinity Ca2+ sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca2+] during IP3-evoked Ca2+ release, but not during SOCE. Most lysosomes associate with endoplasmic reticulum (ER) and dwell at regions populated by IP3R clusters, but IP3Rs do not assemble ER-lysosome contacts. Increasing lysosomal pH does not immediately prevent Ca2+ uptake, but it causes lysosomes to slowly redistribute and enlarge, reduces their association with IP3Rs, and disrupts Ca2+ exchange with ER. In a "piston-like" fashion, ER concentrates cytosolic Ca2+ and delivers it, through large-conductance IP3Rs, to a low-affinity lysosomal uptake system. The involvement of IP3Rs allows extracellular stimuli to regulate Ca2+ exchange between the ER and lysosomes.
dc.format.mediumPrint
dc.identifier.doi10.17863/CAM.34700
dc.identifier.eissn2211-1247
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287396
dc.languageeng
dc.language.isoeng
dc.publisherElsevier BV
dc.publisher.urlhttp://dx.doi.org/10.1016/j.celrep.2018.11.064
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCa(2+)
dc.subjectIP(3) receptor
dc.subjectconcanamycin A
dc.subjectendoplasmic reticulum
dc.subjectgenetically encoded Ca(2+) sensor
dc.subjectlysosome
dc.subjectmembrane contact site
dc.subjectproximity ligation assay
dc.subjectstore-operated Ca(2+) entry
dc.subjectCalcium
dc.subjectCalcium Signaling
dc.subjectCytosol
dc.subjectEndoplasmic Reticulum
dc.subjectHEK293 Cells
dc.subjectHeLa Cells
dc.subjectHumans
dc.subjectHydrogen-Ion Concentration
dc.subjectInositol 1,4,5-Trisphosphate Receptors
dc.subjectLysosomes
dc.titleIP3 Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca2+ to Lysosomes.
dc.typeArticle
dcterms.dateAccepted2018-11-15
prism.endingPage3193.e7
prism.issueIdentifier11
prism.publicationDate2018
prism.publicationNameCell Rep
prism.startingPage3180
prism.volume25
pubs.funder-project-idWellcome Trust (101844/Z/13/Z)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P005330/1)
rioxxterms.licenseref.startdate2018-12
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1016/j.celrep.2018.11.064

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1-s2.0-S2211124718318400-main.pdf
Size:
5.39 MB
Format:
Adobe Portable Document Format
Description:
Published version
Licence
https://creativecommons.org/licenses/by/4.0/
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
DepositLicenceAgreementv2.1.pdf
Size:
150.9 KB
Format:
Adobe Portable Document Format
Download

Collections

Cambridge University Research Outputs