Abstract
BackgroundThe dystroglycan (DG) complex is a major non-integrin cell adhesion system whose multiple biological roles involve, among others, skeletal muscle stability, embryonic development and synapse maturation. DG is composed of two subunits: α-DG, extracellular and highly glycosylated, and the transmembrane β-DG, linking the cytoskeleton to the surrounding basement membrane in a wide variety of tissues. A single copy of the DG gene (DAG1) has been identified so far in humans and other mammals, encoding for a precursor protein which is post-translationally cleaved to liberate the two DG subunits. Similarly, D. rerio (zebrafish) seems to have a single copy of DAG1, whose removal was shown to cause a severe dystrophic phenotype in adult animals, although it is known that during evolution, due to a whole genome duplication (WGD) event, many teleost fish acquired multiple copies of several genes (paralogues).ResultsData mining of pufferfish (T. nigroviridis and T. rubripes) and other teleost fish (O. latipes and G. aculeatus) available nucleotide sequences revealed the presence of two functional paralogous DG sequences. RT-PCR analysis proved that both the DG sequences are transcribed in T. nigroviridis. One of the two DG sequences harbours an additional mini-intronic sequence, 137 bp long, interrupting the uncomplicated exon-intron-exon pattern displayed by DAG1 in mammals and D. rerio. A similar scenario emerged also in D. labrax (sea bass), from whose genome we have cloned and sequenced a new DG sequence that also harbours a shorter additional intronic sequence of 116 bp. Western blot analysis confirmed the presence of DG protein products in all the species analysed including two teleost Antarctic species (T. bernacchii and C. hamatus).ConclusionOur evolutionary analysis has shown that the whole-genome duplication event in the Class Actinopterygii (ray-finned fish) involved also DAG1. We unravelled new important molecular genetic details about fish orthologous DGs, which might help to increase the current knowledge on DG expression, maturation and targeting and on its physiopathological role in higher organisms.
Highlights
The dystroglycan (DG) complex is a major non-integrin cell adhesion system whose multiple biological roles involve, among others, skeletal muscle stability, embryonic development and synapse maturation
Our evolutionary analysis has shown that the whole-genome duplication event in the Class Actinopterygii involved DAG1
With the aim of carrying out an expanded genetic and biochemical comparative analysis, we examined DAG1 from several fish species; besides D. labrax and D. rerio, we analysed pufferfish characterized by compact genomes (T. nigroviridis and T. rubripes), other teleosts such as O. latipes and G. aculeatus, and Antarctic species (T. bernacchii and C. hamatus)
Summary
The dystroglycan (DG) complex is a major non-integrin cell adhesion system whose multiple biological roles involve, among others, skeletal muscle stability, embryonic development and synapse maturation. DG is composed of two subunits: α-DG, extracellular and highly glycosylated, and the transmembrane β-DG, linking the cytoskeleton to the surrounding basement membrane in a wide variety of tissues. A single copy of the DG gene (DAG1) has been identified so far in humans and other mammals, encoding for a precursor protein which is post-translationally cleaved to liberate the two DG subunits. In mammals DAG1 possesses an uncomplicated exon-intron-exon structure, and its transcription and translation generates a precursor protein that is post-translationally cleaved into two noncovalently associated subunits: the highly glycosylated extracellular α-DG and the transmembrane β-DG [1]. In skeletal muscle and in a wide variety of tissues αDG binds extracellular matrix molecules, such as laminins, agrins and perlecan, and interacts non covalently with β-DG, that binds dystrophin via its cytoplasmic tail [3]. The degree of sequence identity among mammals is remarkably high (> 90%), while the recently identified cDNA sequences of X. laevis and D. rerio (zebrafish) confirm that a very high degree of similarity is found in lower vertebrate species [4,5]
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