出版社：American Society for Biochemistry and Molecular Biology
摘要：Recently identified StarD5 belongs to the StarD4 subfamily,a subfamily of steroidogenic acute regulatory related lipidtransfer (START) domain proteins that includes StarD4 and StarD6,proteins whose functions remain unknown. The objective of thisstudy was to confirm StarD5's protein localization and sterolbinding capabilities as measures to pursue function. Using rabbitpolyclonal antibody against newly purified human histidine-tagged/StarD5protein, StarD5 was detected in human liver. In parallel studies,increased expression of StarD5 in primary hepatocytes led toa marked increase in microsomal free cholesterol. Cell fractionationstudies demonstrated StarD5 protein in liver cytosolic fractionsonly, suggesting StarD5 as a directional cytosolic sterol carrier.Supportive in vitro binding assays demonstrated a concentration-dependentbinding of cholesterol by StarD5 similar to that of the cholesterolbinding START domain protein StarD1. In contrast to selectivecholesterol binding by StarD1, StarD5 bound the potent regulatoryoxysterol, 25-hydroxycholesterol, in a concentration-dependentmanner. StarD5 binding appeared selective for cholesterol and25-hydroxycholesterol, as no binding was observed for othertested sterols.
The ability of StarD5 to bind not only cholesterol but also25-hydroxycholesterol, a potent inflammatory mediator and regulatoryoxysterol, raises basic fundamental questions about StarD5'srole in the maintenance of cellular cholesterol homeostasis.Supplementary key words liver • cholesterol • metabolism • steroidogenic acute regulatory related lipid transfer • cholesterol transporter
