title: Human StarD5, a cytosolic StAR-related lipid binding protein.
abstract: Recently identified StarD5 belongs to the StarD4 subfamily, a subfamily of steroidogenic acute regulatory related lipid transfer (START) domain proteins that includes StarD4 and StarD6, proteins whose functions remain unknown. The objective of this study was to confirm StarD5's protein localization and sterol binding capabilities as measures to pursue function. Using rabbit polyclonal antibody against newly purified human histidine-tagged/StarD5 protein, StarD5 was detected in human liver. In parallel studies, increased expression of StarD5 in primary hepatocytes led to a marked increase in microsomal free cholesterol. Cell fractionation studies demonstrated StarD5 protein in liver cytosolic fractions only, suggesting StarD5 as a directional cytosolic sterol carrier. Supportive in vitro binding assays demonstrated a concentration-dependent binding of cholesterol by StarD5 similar to that of the cholesterol binding START domain protein StarD1. In contrast to selective cholesterol binding by StarD1, StarD5 bound the potent regulatory oxysterol, 25-hydroxycholesterol, in a concentration-dependent manner. StarD5 binding appeared selective for cholesterol and 25-hydroxycholesterol, as no binding was observed for other tested sterols. The ability of StarD5 to bind not only cholesterol but also 25-hydroxycholesterol, a potent inflammatory mediator and regulatory oxysterol, raises basic fundamental questions about StarD5's role in the maintenance of cellular cholesterol homeostasis.
authors.affiliation: Department of Medicine, Veterans Affairs Medical Center and Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rodriguez-Agudo
authors.forename: Shunlin
authors.initials: S
authors.lastname: Ren
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.forename: Kaye
authors.initials: K
authors.lastname: Redford
authors.forename: Ramesh
authors.initials: R
authors.lastname: Natarajan
authors.forename: Antonio
authors.initials: A
authors.lastname: Del Castillo
authors.forename: Gregorio
authors.initials: G
authors.lastname: Gil
authors.forename: William M
authors.initials: WM
authors.lastname: Pandak
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry*; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D008099:Liver / Q000737:chemistry; D011485:Protein Binding; D013261:Sterols / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D006888:Hydroxycholesterols; C456546:STARD5 protein, human; D013261:Sterols; C007997:25-hydroxycholesterol; D002784:Cholesterol