Adhesion GPCRs are widely expressed throughout the subsections of the gastrointestinal tract

Luca Badiali,Pawel K Olszewski,Olof Nylander,Jonathan Cedernaes,Helgi B Schiöth,Anna V Vergoni

doi:10.1186/1471-230x-12-134

Luca Badiali, Pawel K Olszewski + Show 4 more

Open Access

https://doi.org/10.1186/1471-230x-12-134

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Abstract

BackgroundG protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. Here we present the first comprehensive anatomical profiling of mRNA expression of all 30 Adhesion GPCRs in the rat GI tract divided into twelve subsegments.MethodsUsing RT-qPCR, we studied the expression of Adhesion GPCRs in the esophagus, the corpus and antrum of the stomach, the proximal and distal parts of the duodenum, ileum, jejunum and colon, and the cecum.ResultsWe found that twenty-one Adhesion GPCRs (70%) had a widespread (expressed in five or more segments) or ubiquitous (expressed in eleven or more segments) distribution, seven (23%) were restricted to a few segments of the GI tract and two were not expressed in any segment. Most notably, almost all Group III members were ubiquitously expressed, while the restricted expression was characteristic for the majority of group VII members, hinting at more specific/localized roles for some of these receptors.ConclusionsOverall, the distribution of Adhesion GPCRs points to their important role in GI tract functioning and defines them as a potentially crucial target for pharmacological interventions.

Highlights

G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target
The rat Adhesion GPCR gene sequences were downloaded from GenBank and 7TM regions were identified with the Conserved Domain Database [33]
Each reaction was run in triplicate and with a positive control to confirm the validity of the amplification process; relative expression values for rat Adhesion GPCRs are displayed as a fold decrease relative to the detected maximum expression, arbitrarily set at 1

Summary

Introduction

G protein-coupled receptors (GPCRs) represent one of the largest families of transmembrane receptors and the most common drug target. The Adhesion subfamily is the second largest one of GPCRs and its several members are known to mediate neural development and immune system functioning through cell-cell and cell-matrix interactions. The distribution of these receptors has not been characterized in detail in the gastrointestinal (GI) tract. The main feature of the Adhesion family is the long N terminus with complex domain architecture which is thought to be highly glycosylated and form a rigid structure in the outer part of the protein This extracellular portion contains the GPCR proteolytic site (GPS) and several various domains that can be found in other proteins such as lectin, epidermal growth factor, olfactomedin, immunoglobulin, thrombospondin and cadherin domains [3]. A few members of Adhesion GPCRs have been demonstrated to interact with G proteins [8,9]

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