title: Subcellular distribution of the 18kDa translocator protein and transcript variant PBR-S in human cells.
abstract: Despite continued interest in the 18kDa translocator protein (PBR/TSPO) as a biomarker and a therapeutic target for a range of diseases, its functional role, such as in the steroid synthesis pathway and energy metabolism has either become contentious or remains to be described more precisely. The PBR/TSPO gene consists of four exons, while a shorter isoform termed PBR-S lacks exon 2. The PBR-S 102-codon open reading frame differs to that of PBR/TSPO, resulting in a protein that is completely unrelated to PBR/TSPO. To our knowledge, PBR-S protein has never been described and has no known or proposed function. To obtain possible clues on the role of this uncharacterised protein, we compared the subcellular distribution of PBR-S to that of PBR/TSPO. By expressing fluorescently tagged PBR/TSPO, we confirmed that full-length PBR/TSPO co-localises with mitochondria in HeLa, HEK-293, MDA-MB-231, BJ and U87-MG human cell lines. Unlike the strictly mitochondrial localisation of PBR/TSPO, PBR-S has a punctate distribution throughout the cytosol that co-localises with lysosomes in HeLa, HEK-293, MDA-MB-231, BJ and U87-MG cells. In summary, within the cell lines examined we confirm mitochondria rather than occasionally reported other localisations, such as the cell nucleus, to be the only site where PBR/TSPO resides. Due to the lack of any shared protein sequences and the different subcellular locations, we suggest that the previously uncharacterised PBR-S protein variant of the PBR/TSPO gene is likely to serve a different yet to be discovered function compared to PBR/TSPO.
authors.affiliation: Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia; National Imaging Facility, Brain and Mind Centre and Faculty of Health Sciences, University of Sydney, Camperdown, NSW 2050, Australia.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Middleton
authors.affiliation: Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia; National Imaging Facility, Brain and Mind Centre and Faculty of Health Sciences, University of Sydney, Camperdown, NSW 2050, Australia. Electronic address: rib@ansto.gov.au.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D008247:Lysosomes / Q000737:chemistry*; D008928:Mitochondria / Q000737:chemistry; D018079:Receptors, GABA / Q000032:analysis* / Q000235:genetics*; D014162:Transfection
chemical_list: D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: Lysosomes; Mitochondria; Putative peripheral benzodiazepine receptor-related protein; TSPO