Elsevier

Genomics

Volume 85, Issue 3, March 2005, Pages 372-385
Genomics

Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors

https://doi.org/10.1016/j.ygeno.2004.11.010Get rights and content

Abstract

Trace amines are endogenous compounds structurally related to classical biogenic amines that have been studied for decades, triggered by their link to psychiatric conditions of high epidemiological and economical relevance. The understanding of their pharmacology on the molecular level was hampered until the recent discovery of trace-amine-specific receptors. We completed the identification of all members of this novel GPCR family in human, chimpanzee, rat, and mouse and observed remarkable interspecies differences, even between human and chimpanzee. The analysis of the chromosomal localizations, phylogenetic relationships, and ligand pocket vectors reveals three distinct receptor subfamilies. As most of these receptors do not respond to trace amines, each subfamily will presumably have a distinct pharmacological profile, which remains to be identified. We propose a uniform nomenclature describing this novel GPCR family in all mammalian species as trace-amine-associated receptors (TAARs), which resolves the ambiguities and contradictions of the previous naming.

Section snippets

A uniform nomenclature for TA and related receptors

Examination of the literature and public database entries revealed numerous inconsistencies with respect to the naming of the receptor family; e.g., Borowsky et al. [6] used the abbreviation TA for some of the TA receptors, while Bunzow et al. [7] designated the same receptors with the symbol TAR, which also refers to the Escherichia coli aspartate receptors [8]. In addition, the human receptor GPR102 [9] is also referred to as TA5 [6], human 5-HT4P [10] has also been named TA2P [6], and GPR57

Discussion

Intense efforts throughout several decades of research directed toward the identification of specialized TA receptors have recently resulted in the identification of a novel family of GPCRs [6], [7]. These specialized TA receptors had so far only been hypothesized based on reported high-affinity TA binding sites in the central nervous system of human and other mammals [20], [21], [22]. With the recent description of specific TA receptors [6], [7] the essential heretofore missing components of

DNA samples and animals

Genomic DNA samples were obtained from the following sources: Human genomic DNA was purchased from Roche Diagnostics (Rotkreuz, Switzerland), genomic DNA from chimpanzee (P. troglodytes) of unknown geographic origin was obtained from the German Primate Center (Goettingen, Germany), genomic DNA from C57BL/6 mice was purchased from The Jackson Laboratory (Bar Harbor, ME, USA), and genomic DNA from Crl:Wi rats was isolated from tail biopsies essentially as described in [31].

RNA employed for cDNA

Acknowledgments

We thank our colleagues Theresa Ballard, Jean-Luc Moreau, Henri Stalder, and Sabine Kolczewski for many stimulating discussions and Danièle Buchy, Agnes Nilly, Sylvie Chaboz, Veit Metzler, and Vincent Boehler for excellent technical help; Clemens Broger for help with analysis of genomic sequences; Christian Roos for kindly providing chimpanzee genomic DNA; and the members of the Human Genome Organization Gene Nomenclature Committee for valuable advice. The authors acknowledge the continued

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