Mining the Arabidopsis thaliana genome for highly-divergent seven transmembrane receptors

Seven-transmembrane (7TM)-region containing proteins constitute the largest receptor superfamily in vertebrates and other metazoans. These cell-surface receptors are activated by a diverse array of ligands, and are involved in various signaling processes, such as cell proliferation, neurotransmission, metabolism, smell, taste, and vision. They are the central players in eukaryotic signal transduction. They are commonly referred to as G protein-coupled receptors (GPCRs) because most transduce extracellular signals into cellular physiological responses through the activation of heterotrimeric guanine nucleotide binding proteins (G proteins) [1]. However, an increasing number of alternative 'G protein-independent' signaling mechanisms have been associated with groups of these 7TM proteins [2-5]. Thus, for precision and clarity, we refer to these proteins simply as 7TM receptors (7TMRs), and candidate proteins in organisms greatly divergent to humans are designated here as 7TM putative receptors (7TMpRs).The human genome encodes approximately 800 or more 7TMRs, both with and without known cognate ligands (the latter are so-called orphan GPCRs); they thus constitute >1% of the gene complement [6,7]. More than 1,000 genes or 5% of the Caenorhabditis elegans genome are predicted to encode 7TMRs; the majority of them appear to be chemoreceptors [8]. Approximately 300 7TMR-encoding genes (about 1% to 2% of the genome) have been recognized in the Drosophila melanogaster genome [6,7]. Compared to such large numbers of 7TMRs found in animal genomes, very few 7TMpRs have been reported in plants and fungi. Only 22 Arabidopsis 7TMpRs have been described so far. Fifteen of them constitute the 'mildew resistance locus O' (MLO) family, whose direct interaction with the G-protein α subunit (Gα) has not been shown [9,10]. While another 7TMpR, GCR1 [11], directly interacts with the plant Gα subunit GPA1 [12], it has been shown that GCR1 can act independently of the heterotrimeric G-prot