Abstract
BackgroundAdhesion G protein-coupled receptors (aGPCRs) are the second largest of the five GPCR families and are essential for a wide variety of physiological processes. Zebrafish have proven to be a very effective model for studying the biological functions of aGPCRs in both developmental and adult contexts. However, aGPCR repertoires have not been defined in any fish species, nor are aGPCR expression profiles in adult tissues known. Additionally, the expression profiles of the aGPCR family have never been extensively characterized over a developmental time-course in any species.ResultsHere, we report that there are at least 59 aGPCRs in zebrafish that represent homologs of 24 of the 33 aGPCRs found in humans; compared to humans, zebrafish lack clear homologs of GPR110, GPR111, GPR114, GPR115, GPR116, EMR1, EMR2, EMR3, and EMR4. We find that several aGPCRs in zebrafish have multiple paralogs, in line with the teleost-specific genome duplication. Phylogenetic analysis suggests that most zebrafish aGPCRs cluster closely with their mammalian homologs, with the exception of three zebrafish-specific expansion events in Groups II, VI, and VIII. Using quantitative real-time PCR, we have defined the expression profiles of 59 zebrafish aGPCRs at 12 developmental time points and 10 adult tissues representing every major organ system. Importantly, expression profiles of zebrafish aGPCRs in adult tissues are similar to those previously reported in mouse, rat, and human, underscoring the evolutionary conservation of this family, and therefore the utility of the zebrafish for studying aGPCR biology.ConclusionsOur results support the notion that zebrafish are a potentially useful model to study the biology of aGPCRs from a functional perspective. The zebrafish aGPCR repertoire, classification, and nomenclature, together with their expression profiles during development and in adult tissues, provides a crucial foundation for elucidating aGPCR functions and pursuing aGPCRs as therapeutic targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1296-8) contains supplementary material, which is available to authorized users.
Highlights
Adhesion G protein-coupled receptors are the second largest of the five GPCR families and are essential for a wide variety of physiological processes
Most Adhesion G protein-coupled receptor (aGPCR) undergo autoproteolysis at the Genomics (2015) 16:62GPCR proteolytic site (GPS) motif, which results in a protein that is separated into an N-terminal fragment (NTF) and C-terminal fragment (CTF) that are thought to remain non-covalently attached at the cell surface [6]
Defining the zebrafish aGPCR repertoire To define the zebrafish aGPCR repertoire, we first compiled a list of nucleotide and protein sequences for 33 aGPCRs annotated in the Zv8 release of the zebrafish genome using three genomic databases: GenBank [24], Ensembl [25], and the zebrafish model organism database (ZFIN) [26]
Summary
Adhesion G protein-coupled receptors (aGPCRs) are the second largest of the five GPCR families and are essential for a wide variety of physiological processes. The “adhesion” classification was given to this family of GPCRs due to the large number of classical cell adhesion domains found in the NTFs of many of these receptors [4,7]. In other proteins, these “adhesion” domains (e.g., EGF-like domains and cadherin domains) are involved in protein-protein, cell-matrix, and cell-cell interactions, leading to the idea that they perform similar functions in aGPCRs [7]. Recent data for multiple aGPCRs suggests that these proteins can function as adhesion molecules by virtue of the NTF, and as classical GPCRs that signal through G-proteins by virtue of the CTF, in addition to the roles the NTF and CTF have in concert with one another [8,9,10,11,12,13]
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