title: The Niemann-Pick C1 and caveolin-1 proteins interact to modulate efflux of low density lipoprotein-derived cholesterol from late endocytic compartments.
abstract: The Niemann-Pick C1 (NPC1) protein has a central role in regulating the efflux of lipoprotein-derived cholesterol from late endosomes/lysosomes and transport to other cellular compartments. Since the NPC1 protein has been shown to regulate the transport of cholesterol to cellular compartments enriched with the ubiquitous cholesterol-binding and transport protein caveolin-1, the present study was performed to determine whether the NPC1 and caveolin-1 proteins interact and function to modulate efflux of low density lipoprotein (LDL)-derived cholesterol from endocytic compartments. To perform these studies, normal human fibroblasts were grown in media with lipoprotein-deficient serum (LPDS) or media with LPDS supplemented with purified human LDL. The results indicated reciprocal co-immunoprecipitation and partial co-localization of the NPC1 and caveolin-1 proteins that was decreased when fibroblasts were grown in media with LDL. Consistent with interaction of the NPC1 and caveolin-1 proteins, a highly conserved caveolin-binding motif was identified within a cytoplasmic loop located adjacent to the sterol-sensing domain (SSD) of the NPC1 protein. To examine the functional relevance of this interaction, fibroblasts were transfected with caveolin-1 siRNA and found to accumulate increased amounts of LDL-derived cholesterol within late endosomes/ lysosomes. Together, this report presents novel results demonstrating that the NPC1 and caveolin-1 proteins interact to modulate efflux of LDL-derived cholesterol from late endocytic compartments.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, US.
authors.forename: David
authors.initials: D
authors.lastname: Jelinek
authors.affiliation: Department of Pediatrics, School of Medicine, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, US.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Heidenreich
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, US.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Orlando
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center, Albuquerque, New Mexico, US.
authors.forename: William S
authors.initials: WS
authors.lastname: Garver