Family of human oxysterol binding protein (OSBP) homologues: a novel member implicated in brain sterol metabolism

Oxysterol binding protein (OSBP) is a cytosolic protein that undergoes liga nd-induced binding to the Golgi apparatus and has been implicated in the re gulation of cellular cholesterol metabolism. In the yeast Saccharomyces cer evisiae an OSBP homologue is involved in membrane trafficking through the G olgi complex. Prompted by the multitude of OSBP-related genes in the yeast genome, we carried out a search for human expressed sequence tags (ESTs) di splaying homology to the sterol-binding domain of OSBP. This revealed a min imum of six novel OSBP-related proteins, designated ORP-1 to ORP-6. ORP cDN A probes were generated by reverse transcription-PCR from human liver mRNA and used for Northern blot analysis of human tissue transcript panels. This verifi\ed that each of them represents a different gene product and showed that they display distinct tissue-specific expression patterns. The ORP-1 and -2 mRNA expression levels were similar to or higher than that of OSBP w hile the ORP-3 to -6 mRNAs were detected at lower levels in specific tissue s. The most abundantly expressed new gene, ORP-1, was transcribed at striki ngly high levels in the cortical areas of human brain and displayed sterol- regulated expression in a cultured human neuroblastoma cell Line. This indi cates that ORP-1 may play an important role in maintaining the sterol balan ce in cells of the central nervous system. Together with OSBP, the identifi ed gene products constitute a novel human protein family that may provide a link between organellar sterol status and membrane dynamics.