title: Role of STARD4 and NPC1 in intracellular sterol transport.
abstract: Cholesterol plays an important role in determining the biophysical properties of membranes in mammalian cells, and the concentration of cholesterol in membranes is tightly regulated. Cholesterol moves among membrane organelles by a combination of vesicular and nonvesicular transport pathways, but the details of these transport pathways are not well understood. In this review, we discuss the mechanisms for nonvesicular sterol transport with an emphasis on the role of STARD4, a small, soluble, cytoplasmic sterol transport protein. STARD4 can rapidly equilibrate sterol between membranes, especially membranes with anionic lipid headgroups. We also discuss the sterol transport in late endosomes and lysosomes, which is mediated by a soluble protein, NPC2, and a membrane protein, NPC1. Homozygous mutations in these proteins lead to a lysosomal lipid storage disorder, Niemann-Pick disease type C. Many of the disease-causing mutations in NPC1 are associated with degradation of the mutant NPC1 proteins in the endoplasmic reticulum. Several histone deacetylase inhibitors have been found to rescue the premature degradation of the mutant NPC1 proteins, and one of these is now in a small clinical trial.
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.|Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Maxfield
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.|Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Iaea
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.|Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Nina H
authors.initials: NH
authors.lastname: Pipalia
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D000077296:Niemann-Pick C1 Protein; D013261:Sterols / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; C456544:STARD4 protein, human; D013261:Sterols
keywords: Niemann–Pick C; STARD4; cholesterol; lipid transport proteins; lipoproteins; lipoprotéines; protéines de transport des lipides