An Oxysterol-Binding Protein Family Identified in the Mouse

Abstract

Oxysterols are oxygenated derivatives of cholesterol. They have been shown to influence a variety of biological functions including sterol metabolism, lipid trafficking, and apoptosis. Recently, 12 human OSBP-related genes have been identified. In this study, we have identified a family of 12 oxysterol-binding protein (OSBP)-related proteins (ORPs) in the mouse. A high level of amino acid identity (88-97%) was determined between mouse and human ORPs, indicating a very high degree of evolutionary conservation. All proteins identified contained the conserved OSBP amino acid sequence signature motif "EQVSHHPP," and most contained a pleckstrin homology (PH) domain. Using RT-PCR, each mouse ORP gene was found to exhibit a unique tissue distribution with many showing high expression in testicular, brain, and heart tissues. Interestingly, the tissue distribution of ORP-4 and ORP-10 were the most selective within the family. Expression of the various ORP genes was also investigated, specifically in highly purified populations of hemopoietic precursor cells defined by the lin(-) c-kit(+) Sca-1(+) (LKS(+)) and lin(-) c-kit(+) Sca-1(-) (LKS(-)) immunophenotype. Most ORP genes were expressed in both LKS(+) and LKS(-) populations, although ORP-4 appeared to be more highly expressed in the primitive, stem-cell enriched LKS(+) population, whereas ORP-10 was more highly expressed by maturing LKS(-) cells. The identification of a family of ORP proteins in the mouse, the frequently preferred animal model for in vivo studies, should further our understanding of the function of these proteins and their interactions with each other.

A Detour for Yeast Oxysterol Binding Proteins

“…OSBP is representative of the larger ORP superfamily that is conserved from yeast to man (13)(14)(15)(16), and as discussed below, these proteins bind a variety of sterols. As might be expected of a STP, OSBP shuttles between cellular compartments in response to sterol binding (17)(18)(19).…”

Lessons from comparative analysis of species-specific imprinted genes

“…Furthermore, Osbpl1 and Osbpl2 are fl anked by Lama3 encoding nuclear lamin A and its paralogue Lama5 , respectively, in a tail-to-tail manner. The oxysterol-binding protein (OSBP) family consists of 12 OSBP-related cognate genes (Anniss et al, 2002), most of which encode the Pleckstrin homology (PH) domain and the OSBP domain at amino and carboxyl termini, respectively. The sole anomaly is Osbpl2 which lacks the PH domain (Jaworski et al, 2001).…”

Sterol binding by OSBP-related protein 1L regulates late endosome motility and function

“…These proteins, designated OSBP-related (ORP), OSBPlike (OSBPL) or OSBP homologue (Osh) proteins, have mainly been studied in mammalian and S. cerevisiae systems and are shown to be involved in the control of cellular lipid metabolism, vesicle transport, and cell signaling (reviewed by [11][12][13]. In mammals, the family consists of 12 members [14][15][16], and in yeast, of 7 members [17].…”