Synucleins are a family of conserved proteins expressed abundantly in vertebrate neurons. Mammals express α-, β- and γ- synucleins, of which α-synuclein has received most attention, because of its involvement in the pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). However, the cellular roles of synucleins in health and disease are poorly understood. The purpose of this study was to characterize zebrafish synucleins in order to provide a novel in vivo system in which to study their neuronal functions.In zebrafish, we found three synuclein genes, which we designated sncb, sncg1 and sncg2, and which respectively encode an orthologue of mammalian β-synuclein, and dual paralogues of mammalian γ-synuclein. In contrast to other fish species, no α-synuclein orthologue was found, either by interrogation of available sequence databases, or by a variety of molecular techniques deployed to clone a putative snca cDNA from brain tissue. Syntenic analysis showed that orthologues of several genes flanking mammalian SNCA were absent from the zebrafish genome, suggesting that deletion of the ancestral snca locus may have occurred during evolution of zebrafish. A single sncb transcript of 1.6kb was expressed in the nervous system from 12 hours post fertilization (hpf) through adulthood, and a single sncg1 transcript of 3.4kb from 24hpf through adulthood. The alternatively spliced sncg2 transcript was detected abundantly in the notochord during development and weakly in the adult brain. Discrete expression patterns of sncb and sncg1 were found in the mature CNS: sncb was prominently expressed in the forebrain and in the diencephalon; while sncg1 showed robust expression in the medulla and cerebellum. Both synucleins were expressed in dopaminergic neurons, suggesting a potential functional role for these proteins in catecholaminergic systems.Our detailed characterization of zebrafish synucleins adds to understanding the evolution of this family of proteins, and provides resources for in vivo functional studies exploiting molecular techniques that can be readily applied in the zebrafish.
Characterization of zebrafish synucleins
Milanese, Chiara;
2010-01-01
Abstract
Synucleins are a family of conserved proteins expressed abundantly in vertebrate neurons. Mammals express α-, β- and γ- synucleins, of which α-synuclein has received most attention, because of its involvement in the pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). However, the cellular roles of synucleins in health and disease are poorly understood. The purpose of this study was to characterize zebrafish synucleins in order to provide a novel in vivo system in which to study their neuronal functions.In zebrafish, we found three synuclein genes, which we designated sncb, sncg1 and sncg2, and which respectively encode an orthologue of mammalian β-synuclein, and dual paralogues of mammalian γ-synuclein. In contrast to other fish species, no α-synuclein orthologue was found, either by interrogation of available sequence databases, or by a variety of molecular techniques deployed to clone a putative snca cDNA from brain tissue. Syntenic analysis showed that orthologues of several genes flanking mammalian SNCA were absent from the zebrafish genome, suggesting that deletion of the ancestral snca locus may have occurred during evolution of zebrafish. A single sncb transcript of 1.6kb was expressed in the nervous system from 12 hours post fertilization (hpf) through adulthood, and a single sncg1 transcript of 3.4kb from 24hpf through adulthood. The alternatively spliced sncg2 transcript was detected abundantly in the notochord during development and weakly in the adult brain. Discrete expression patterns of sncb and sncg1 were found in the mature CNS: sncb was prominently expressed in the forebrain and in the diencephalon; while sncg1 showed robust expression in the medulla and cerebellum. Both synucleins were expressed in dopaminergic neurons, suggesting a potential functional role for these proteins in catecholaminergic systems.Our detailed characterization of zebrafish synucleins adds to understanding the evolution of this family of proteins, and provides resources for in vivo functional studies exploiting molecular techniques that can be readily applied in the zebrafish.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
