Published ahead of print on June 9, 2005, doi:10.1165/rcmb.2004-0405OC Am. J. Respir. Cell Mol. Biol., Volume 33, Number 3, September 2005, 262-270 A more recent version of this article appeared on September 1, 2005
Submitted on December 15, 2004 Characterization of GPRA, a Novel G Protein-coupled Receptor Related to AsthmaJohanna Vendelin1,1 Department of Medical Genetics, University of Helsinki, Helsinki, Finland, 2 GeneOS Ltd., Helsinki, Finland, 3 Department of Pathology, University of Helsinki, Helsinki, Finland, 4 Department of Anatomy, University of Helsinki, Helsinki, Finland, 5 Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, 6 Department of Medical Genetics, University of Helsinki, Helsinki, Finland; Department of Biosciences at Novum and Clinical Research Centre, Karolinska Institutet, Huddinge, Sweden, 7 Department of Medical Genetics, University of Helsinki, Helsinki, Finland; GeneOS Ltd., Helsinki, Finland * To whom correspondence should be addressed. E-mail: tarja.laitinen{at}geneos.fi.
We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembranes topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth.
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