Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function

doi:10.1016/j.tips.2006.06.005

Trends in Pharmacological Sciences

Volume 27, Issue 8, August 2006, Pages 402-409

https://doi.org/10.1016/j.tips.2006.06.005 Get rights and content

The peripheral-type benzodiazepine receptor or recognition site (PBR) is a widely distributed transmembrane protein that is located mainly in the outer mitochondrial membrane. The PBR binds to high-affinity drug ligands and cholesterol. Many functions are associated directly or indirectly with the PBR, including the regulation of cholesterol transport and the synthesis of steroid hormones, porphyrin transport and heme synthesis, apoptosis, cell proliferation, anion transport, regulation of mitochondrial functions and immunomodulation. Based on these functions, there are many potential clinical applications of PBR modulation, such as in oncologic, endocrine, neuropsychiatric and neurodegenerative diseases. Although ‘PBR’ is a widely used and accepted name in the scientific community, recent data regarding the structure and molecular function of this protein increasingly support renaming it to represent more accurately its subcellular role (or roles) and putative tissue-specific function (or functions). Translocator protein (18 kDa) is proposed as a new name, regardless of the subcellular localization of the protein.

Section snippets

Overview of the peripheral-type benzodiazepine receptor or recognition site

The peripheral-type benzodiazepine receptor or recognition site (PBR) was identified in 1977 when investigators were searching for binding sites for the benzodiazepine diazepam in peripheral tissues 1, 2, 3. The early characterization of these diazepam-binding sites outside the brain led to their assignment as ‘peripheral-type’ benzodiazepine receptors, or PBRs, to distinguish them from the central benzodiazepine receptor, which is part of the GABA_A receptor complex 2, 3.

Although the term ‘PBR’

Fundamental functions attributed to the PBR based on structure–function relationships

Evidence supports three main potential structure–function relationships for the PBR (Table 1): (i) cholesterol binding followed by cholesterol transport, which is crucial in steroid and bile salt biosynthesis; (ii) protein import, which is important for membrane biogenesis; and (iii) porphyrin binding and transport, which is involved in heme biosynthesis. All other identified functions of the PBR might be brought about, directly or indirectly, by its cholesterol- and/or porphyrin-binding

The PBR in animal models of disease and in human pathology

The PBR is involved in different pathological conditions such as ischemia–reperfusion injury 45, 46, brain injury 2, 31, certain forms of epilepsy 2, 31, 47, neurodegenerative disorders (e.g. Alzheimer's disease 2, 31 and Parkinson's disease [31]) and peripheral neuropathy [48] (Table 1). However, the bulk of the research efforts regarding the involvement of the PBR in human disease has focused on two therapeutic areas: oncology and psychiatry.

Imaging

The development of positron emission tomography techniques using PBR radioligands 59, 60 has facilitated the evaluation of the expression and distribution of the PBR in mice, rats, primates and humans. These techniques were used to demonstrate the role of the PBR as a specific and sensitive marker for the visualization and quantification of neuropathological changes in the CNS [61].

PBR-independent effects of PBR ligands

Many of the functions attributed to the PBR have been established using high-affinity drug ligands. Although, in some cases, these studies were complemented by others in which the manipulation of PBR expression was linked to functional changes in, for example, cholesterol binding, steroid biosynthesis and cell proliferation 3, 35, 56, in many cases no such evidence was provided. Indeed, it was recently shown that the action of a PBR drug ligand on a cell system (its function) might not be

Renaming the PBR

Although the name ‘PBR’ is widely accepted in the scientific community, the renaming of this protein to represent more accurately recent findings regarding its structure, subcellular roles and putative functions is warranted. We formed a working group and reached a consensus on a new name: translocator protein (18 kDa) (TSPO), which applies to the protein regardless of its localization.

Concluding remarks

The new name ‘translocator protein (18 kDa)’, or ‘TSPO’, addresses the shortcomings and misrepresentations of the previous names of this protein while more accurately representing its subcellular roles and putative molecular functions. This name provides the required specificity while enabling enough flexibility to tailor the name depending on the location of the protein. Thus, we propose the names ‘mitochondrial translocator protein (18 kDa)’ (‘mitoTSPO’) and ‘nuclear translocator protein (18

Acknowledgements

We thank Elspeth Bruford (HGNC) and HGNC for assistance and guidance with the proposed new nomenclature, and Leo Veenman (Bruce Rappaport Family Institute for Research in the Medical Sciences) and Gary Weisinger (Tel Aviv University Sourasky Medical Center) for helpful comments. We apologize to many of our colleagues whose work is not cited or is cited indirectly owing to space limitations. The work of the ‘working group for renaming the PBR’ was supported by Novartis Pharmaceuticals. We thank

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Trends in Pharmacological Sciences

OpinionTranslocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function

Section snippets

Overview of the peripheral-type benzodiazepine receptor or recognition site

Fundamental functions attributed to the PBR based on structure–function relationships

The PBR in animal models of disease and in human pathology

Imaging

PBR-independent effects of PBR ligands

Renaming the PBR

Concluding remarks

Acknowledgements

Steroids

Biochem. Biophys. Res. Commun.

Life Sci.

Eur. J. Pharmacol.

Mol. Cell. Endocrinol.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Neurobiol. Aging

Life Sci.

J. Steroid Biochem. Mol. Biol.

FEBS Lett.

Life Sci.

Neuroscience

Exp. Cell Res.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Pharmacol.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Reprod. Toxicol.

Brain Res.

Mech. Ageing Dev.

Biol. Psychiatry

Biol. Psychiatry

J. Psychiatr. Res.

Biochem. Pharmacol.

Lancet

Biochem. Pharmacol.

Pharmacol. Ther.

High densities of benzodiazepine receptors in human cortical areas

Nature

Enigma of the peripheral benzodiazepine receptor

Pharmacol. Rev.

A novel Arabidopsis thaliana protein is a functional peripheral-type benzodiazepine receptor

Plant Cell Physiol.

Opinion
Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function