PDZK1 is required for maintaining hepatic scavenger receptor, class B, type I (SR-BI) steady state levels but not its surface localization or function

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dc.contributor.authorYesilaltay, Ayce
dc.contributor.authorKocher, Olivier
dc.contributor.authorPal, Rinku
dc.contributor.authorLeiva, Andrea
dc.contributor.authorQuinones, Veronica
dc.contributor.authorRigotti, Attilio
dc.contributor.authorKrieger, Monty
dc.date.accessioned2024-01-10T13:51:55Z
dc.date.available2024-01-10T13:51:55Z
dc.date.issued2006
dc.description.abstractPDZK1 is a multi-PDZ domain-containing adaptor protein that binds to the C terminus of the high density lipoprotein receptor, scavenger receptor, class B, type I (SR-BI), and controls the posttranscriptional, tissue-specific expression of this lipoprotein receptor. In the absence of PDZK1 (PDZK1(-/-) mice), murine hepatic SR-BI protein levels are very low (< 5% of control). As a consequence, abnormal plasma lipoprotein metabolism (similar to 1.5-1.7-fold increased total plasma cholesterol carried in both normal size and abnormally large high density lipoprotein particles) resembles, but is not as severely defective as, that in SR-BI(-/-) mice. Here we show that the total plasma cholesterol levels and size distribution of lipoproteins are virtually identical in SR-BI(-/-) and SR-BI(-/-)/ PDZK1(-/-) mice, indicating that most, if not all of the effects of PDZK1 on lipoprotein metabolism are likely because of the effects of PDZK1 on SR-BI. Hepatic overexpression of wild-type SR-BI in PDZK1(-/-) mice restored near or greater than normal levels of cell surface-expressed, functional SR-BI protein levels in the livers of SR-BI(-/-)/ PDZK1(-/-) mice and consequently restored apparently normal lipoprotein metabolism in the absence of PDZK1. Thus, PDZK1 is important for maintaining adequate steady state levels of SR-BI in the liver but is not essential for cell surface expression or function of hepatic SR-BI.
dc.description.funderFOGARTY INTERNATIONAL CENTER
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderFIC NIH HHS
dc.description.funderNHLBI NIH HHS
dc.fechaingreso.objetodigital2024-05-14
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M603802200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.pubmedidMEDLINE:16867981
dc.identifier.urihttps://doi.org/10.1074/jbc.M603802200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79633
dc.identifier.wosidWOS:000240680500052
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.issue.numero39
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final28980
dc.pagina.inicio28975
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsregistro bibliográfico
dc.subjectHIGH-DENSITY-LIPOPROTEIN
dc.subjectDOMAIN-CONTAINING PROTEIN
dc.subjectTARGETED DISRUPTION
dc.subjectLIPID-METABOLISM
dc.subjectFREE-CHOLESTEROL
dc.subjectEXPRESSION
dc.subjectHDL
dc.subjectIDENTIFICATION
dc.subjectLIVER
dc.subjectGENE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePDZK1 is required for maintaining hepatic scavenger receptor, class B, type I (SR-BI) steady state levels but not its surface localization or function
dc.typeartículo
dc.volumen281
sipa.codpersvinculados68489
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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