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dc.contributor.authorCanaff, Lucie
dc.contributor.authorErcan, Oya
dc.contributor.authorGrant, Michael
dc.contributor.authorKumar, Ujendra
dc.contributor.authorHendy, Geoffrey N.
dc.contributor.authorPidasheva, Svetlana
dc.date.accessioned2021-03-05T20:39:12Z
dc.date.available2021-03-05T20:39:12Z
dc.date.issued2006
dc.identifier.citationPidasheva S., Grant M., Canaff L., Ercan O., Kumar U., Hendy G. N. , "Calcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly", HUMAN MOLECULAR GENETICS, cilt.15, ss.2200-2209, 2006
dc.identifier.issn0964-6906
dc.identifier.othervv_1032021
dc.identifier.otherav_d530200d-6da6-4cea-ada0-6923f5901ec0
dc.identifier.urihttp://hdl.handle.net/20.500.12627/140680
dc.identifier.urihttps://doi.org/10.1093/hmg/ddl145
dc.description.abstractCalcium-sensing receptor (CASR), expressed in parathyroid gland and kidney, is a critical regulator of extracellular calcium homeostasis. This G protein-coupled receptor exists at the plasma membrane as a homodimer, although it is unclear at which point in the biosynthetic pathway dimerization occurs. To address this issue, we have analyzed wild-type and mutant CASRs harboring R66H, R66C or N583X-inactivating mutations identified in familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroid patients, which were transiently expressed in kidney cells. All mutants were deficient in cell signaling responses to extracellular CASR ligands relative to wild-type. All mutants, although as well expressed as wild-type, lacked mature glycosylation, indicating impaired trafficking from the endoplasmic reticulum (ER). Dimerized forms of wild-type, R66H and R66C mutants were present, but not of the N583X mutant. By immunofluorescence confocal microscopy of non-permeabilized cells, although cell surface expression was observed for the wild-type, little or none was seen for the mutants. In permeabilized cells, perinuclear staining was observed for both wild-type and mutants. By colocalization fluorescence confocal microscopy, the mutant CASRs were localized within the ER but not within the Golgi apparatus. By the use of photobleaching fluorescence resonance energy transfer microscopy, it was demonstrated that the wild-type, R66H and R66C mutants were dimerized in the ER, whereas the N583X mutant was not. Hence, constitutive CASR dimerization occurs in the ER and is likely to be necessary, but is not sufficient, for exit of the receptor from the ER and trafficking to the cell surface.
dc.language.isoeng
dc.subjectYaşam Bilimleri
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSitogenetik
dc.subjectTemel Bilimler
dc.subjectDahili Tıp Bilimleri
dc.subjectTıbbi Genetik
dc.subjectSağlık Bilimleri
dc.subjectTıp
dc.subjectGENETİK VE HAYAT
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectBİYOKİMYA VE MOLEKÜLER BİYOLOJİ
dc.titleCalcium-sensing receptor dimerizes in the endoplasmic reticulum: biochemical and biophysical characterization of CASR mutants retained intracellularly
dc.typeMakale
dc.relation.journalHUMAN MOLECULAR GENETICS
dc.contributor.department, ,
dc.identifier.volume15
dc.identifier.issue14
dc.identifier.startpage2200
dc.identifier.endpage2209
dc.contributor.firstauthorID179199


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