Overexpression of the PDZ1 domain of PDZK1 blocks the activity of hepatic scavenger receptor, class B, type I by altering its abundance and cellular localization

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dc.contributor.authorFenske, Sara A.
dc.contributor.authorYesilaltay, Ayce
dc.contributor.authorPal, Rinku
dc.contributor.authorDaniels, Kathleen
dc.contributor.authorRigotti, Attilio
dc.contributor.authorKrieger, Monty
dc.contributor.authorKocher, Olivier
dc.date.accessioned2024-01-10T12:41:12Z
dc.date.available2024-01-10T12:41:12Z
dc.date.issued2008
dc.description.abstractPDZK1 is a four-PDZ domain-containing scaffold protein that, via its first PDZ domain (PDZ1), binds to the C terminus of the high density lipoprotein (HDL) receptor scavenger receptor, class B, type I (SR-BI). Abolishing PDZK1 expression in PDZK1 knock-out (KO) mice leads to a post-transcriptional, tissue-specific decrease in SR-BI protein level and an increase in total plasma cholesterol carried in abnormally large HDL particles. Here we show that, although hepatic overexpression of PDZK1 restored normal SR-BI protein abundance and function in PDZK1 KO mice, hepatic overexpression of only the PDZ1 domain was not sufficient to restore normal SR-BI function. In wild-type mice, overexpression of the PDZ1 domain overcame the activity of the endogenous hepatic PDZK1, resulting in a 75% reduction in hepatic SR-BI protein levels and intracellular mislocalization of the remaining SR-BI. As a consequence, the plasma lipoproteins in PDZ1 transgenic mice resembled those in PDZK1 KO mice (hypercholesterolemia due to large HDL). These results indicate that the PDZ1 domain can control the abundance and localization, and therefore the function, of hepatic SR-BI and that structural features of PDZK1 in addition to its SR-BI-binding PDZ1 domain are required for normal hepatic SR-BI regulation.
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.description.funderNHLBI NIH HHS
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent8 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M800029200
dc.identifier.eissn1083-351X
dc.identifier.issn0021-9258
dc.identifier.pubmedidMEDLINE:18544532
dc.identifier.urihttps://doi.org/10.1074/jbc.M800029200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77393
dc.identifier.wosidWOS:000258114700028
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.issue.numero32
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final22104
dc.pagina.inicio22097
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectHIGH-DENSITY-LIPOPROTEIN
dc.subjectSR-BI
dc.subjectTARGETED DISRUPTION
dc.subjectCHOLESTEROL EFFLUX
dc.subjectLIPID-METABOLISM
dc.subjectAPOLIPOPROTEIN-E
dc.subjectHDL CHOLESTEROL
dc.subjectEXPRESSION
dc.subjectPROTEIN
dc.subjectGENE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleOverexpression of the PDZ1 domain of PDZK1 blocks the activity of hepatic scavenger receptor, class B, type I by altering its abundance and cellular localization
dc.typeartículo
dc.volumen283
sipa.codpersvinculados68489
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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