Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) Proteins in Non-vesicular Cholesterol Transport

Abstract

Lipid transfer proteins play an important role in non-vesicular transport of sterols, phospholipids, and sphingolipids among intracellular membranes to maintain the proper sterol and lipid distribution. The steroidogenic acute regulatory protein-related lipid transfer (START) domain family are defined by a conserved 210 amino acid sequence that folds into an α/β helix-grip structure containing a hydrophobic pocket for ligand binding. The mammalian START proteins bind a variety of ligands, including cholesterol, phospholipids, sphingolipids, and bile acids with putative roles in non-vesicular lipid transport, tumor suppression, and thioesterase activity. However, the functions of many START proteins have yet to be well characterized. Recent studies have focused on determining the cell type distribution and expression profile of the START proteins, examining the ligand specificity and directionality of transport and characterizing disease states that may be associated with deregulation of START proteins. This chapter will summarize current findings regarding the physiologic and pathological roles of the START proteins in non-vesicular lipid transport.