Normal Hepatic Cell Surface Localization of the High Density Lipoprotein Receptor, Scavenger Receptor Class B, Type I, Depends on All Four PDZ Domains of PDZK1

Simple item page
dc.contributor.authorFenske, Sara A.
dc.contributor.authorYesilaltay, Ayce
dc.contributor.authorPal, Rinku
dc.contributor.authorDaniels, Kathleen
dc.contributor.authorBarker, Caroline
dc.contributor.authorQuinones, Veronica
dc.contributor.authorRigotti, Attilio
dc.contributor.authorKrieger, Monty
dc.contributor.authorKocher, Olivier
dc.date.accessioned2024-01-10T12:40:57Z
dc.date.available2024-01-10T12:40:57Z
dc.date.issued2009
dc.description.abstractPDZK1 is a four PDZ domain-containing scaffold protein that binds to scavenger receptor class B, type I (SR-BI), the high density lipoprotein receptor, by its first PDZ domain (PDZ1). PDZK1 knock-out mice exhibit a >95% decrease in hepatic SR-BI protein and consequently an similar to 70% increase in plasma cholesterol in abnormally large high density lipoprotein particles. These defects are corrected by hepatic overexpression of full-length PDZK1 but not the PDZ1 domain alone, which partially restores SR-BI protein abundance but not cell surface expression or function. We have generated PDZK1 knock-out mice with hepatic expression of four PDZK1 transgenes encoding proteins with nested C-terminal truncations: pTEM, which lacks the three C-terminal residues (putative PDZ-binding motif), and PDZ1.2, PDZ1.2.3, or PDZ1.2.3.4, which contain only the first two, three, or four N-terminalPDZ domains, respectively, but not the remaining C-terminal sequences. Hepatic overexpression of pTEM restored normal hepatic SR-BI abundance, localization, and function. Hepatic overexpression of PDZ1.2 or PDZ1.2.3 partially restored SR-BI abundance (similar to 12 or similar to 30% of wild type, respectively) but did not (PDZ1.2) or only slightly (PDZ1.2.3) restored hepatic SR-BI cell surface localization and function. Hepatic overexpression of PDZ1.2.3.4 completely restored SR-BI protein abundance, cell surface expression, and function (normalization of plasma cholesterol levels). Thus, all four PDZ domains in PDZK1, but not PDZ1-3 alone, are sufficient for its normal control of the abundance, localization, and therefore function of hepatic SR-BI, whereas the residues C-terminal to the PDZ4 domain, including the C-terminal putative PDZ-binding domain, are not required.
dc.description.funderNational Institutes of Health
dc.description.funderClinical Translational Science Award
dc.description.funderFondo Nacional de Desarrollo Cientifico y Tecnologico
dc.description.funderNATIONAL CENTER FOR RESEARCH RESOURCES
dc.description.funderNATIONAL HEART, LUNG, AND BLOOD INSTITUTE
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M808211200
dc.identifier.eissn1083-351X
dc.identifier.pubmedidMEDLINE:19116202
dc.identifier.urihttps://doi.org/10.1074/jbc.M808211200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77365
dc.identifier.wosidWOS:000263560600043
dc.information.autorucMedicina;Quiñones V;S/I;1002010
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.issue.numero9
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final5806
dc.pagina.inicio5797
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectSR-BI
dc.subjectCHYLOMICRON METABOLISM
dc.subjectTARGETED DISRUPTION
dc.subjectCHOLESTEROL EFFLUX
dc.subjectCONTAINING PROTEIN
dc.subjectLIPID-METABOLISM
dc.subjectAPOLIPOPROTEIN-E
dc.subjectEXPRESSION
dc.subjectMICE
dc.subjectLIVER
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleNormal Hepatic Cell Surface Localization of the High Density Lipoprotein Receptor, Scavenger Receptor Class B, Type I, Depends on All Four PDZ Domains of PDZK1
dc.typeartículo
dc.volumen284
sipa.codpersvinculados1002010
sipa.codpersvinculados68489
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
The Journal of Biological Chemistry - 2009 - Normal Hepatic Cell Surface Localization of the High Density Lipoprotein Receptor.pdf
Size:
1.96 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Artículos de revistas