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- The oxysterol-binding protein (OSBP)-related proteins (ORPs) are a family of lipid transfer proteins (LTPs). Concretely, they constitute a family of sterol and phosphoinositide binding and transfer proteins in eukaryotes that are conserved from yeast to humans. They are implicated in many cellular processes related with oxysterol, including signaling, vesicular trafficking, lipid metabolism, and nonvesicular sterol transport. In yeast cells, some ORPs might function as sterol or lipid transporters though yeast strains lacking ORPs do not have significant defects in sterol transport between the endoplasmic reticulum and the plasma membrane. Although sterol transfer is proposed to occur at regions where organelle membranes are closely apposed, disruption of endoplasmic reticulum-plasma membrane contact sites do not have major effects on sterol transfer, though phospholipid homeostasis is perturbed. Various ORPs confine at membrane contacts sites (MCS), where endoplasmic reticulum (ER) is apposed with other organelle limiting membranes. Yeast ORPs also participate in vesicular trafficking, in which they affect Sec14-dependent Golgi vesicle biogenesis and, later in post-Golgi exocytosis, they affect exocyst complex-dependent vesicle tethering to the plasma membrane. In mammalian cells, some ORPs function as sterol sensors that regulate the assembly of protein complexes in response to changes in cholesterol levels. By that means, ORPs most likely affect organelle membrane lipid compositions, with impacts on signaling and vesicle transport, but also cellular lipid metabolism. Oxysterol is a cholesterol metabolite that can be produced through enzymatic or radical processes. Oxysterols, that are the 27-carbon products of cholesterol oxidation by both enzymic and non-enzymic mechanisms, constitute a large family of lipids involved in a plethora of physiological processes. Studies identifying the specific cellular targets of oxysterol indicate that several oxysterols may be regulators of cellular lipid metabolism via control of gene transcription. In addition, they were shown to be involved in other processes such as immune regulatory functions and brain homeostasis. (en)
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