Piccolo paralogs and orthologs display conserved patterns of alternative splicing within the C2A and C2B domains
العنوان: | Piccolo paralogs and orthologs display conserved patterns of alternative splicing within the C2A and C2B domains |
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المؤلفون: | Steven D. Fenster, Lindsey Knapp, Mason Posner, David I. Fountain, Keith Daniel Baugh |
المصدر: | Genes & Genomics. 38:407-419 |
بيانات النشر: | Springer Science and Business Media LLC, 2015. |
سنة النشر: | 2015 |
مصطلحات موضوعية: | 0301 basic medicine, Genetics, animal structures, Alternative splicing, Biology, biology.organism_classification, Biochemistry, Exon skipping, 03 medical and health sciences, Exon, 030104 developmental biology, Gene duplication, Synaptic signaling, Molecular Biology, Zebrafish, Presynaptic active zone, Genomic organization |
الوصف: | Piccolo is an organizational component of the presynaptic active zone, a specialized region of nerve terminals where synaptic vesicles fuse and release their neurotransmitter contents. Alternative splicing (AS) of the mouse Piccolo gene (PCLO) produces two primary splice isoforms: isoform-1 that includes two C2 domains (C2A and C2B) and isoform-2 with only C2A. Genome-wide association studies have identified variations located in or near the C2A domain of human Piccolo that predispose individuals to affective disorders and in rare cases leads to altered brain development. In zebrafish a genome duplication event led to the generation of PCLO-a and PCLO-b: gene paralogs that display strikingly similar genomic organization with other PCLO orthologs. Given this conservation in genomic structure, it is likely that AS patterns of zebrafish PCLO paralogs are similar to mammalian PCLO. We used a RT-PCR strategy to identify four zebrafish isoforms generated from zebrafish PCLO-a and PCLO-b that are equivalent to mouse Piccolo isoform-1 and isoform-2. Additionally, we identified an exon skipping event that leads to exclusion of a 27 nucleotide exon in both zebrafish Piccolo-a and Piccolo-b. Elimination of this exon in mammalian Piccolo alters the calcium binding property of the C2A domain. We also measured transcriptional levels of mouse and zebrafish Piccolo splice variants and demonstrate that despite similarities in AS, there are quantitative differences in gene expression. Our results indicate that AS of Piccolo is similar across diverse taxa and further support the use of zebrafish to study the role of Piccolo in neurodevelopment and synaptic signaling. |
تدمد: | 2092-9293 1976-9571 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::9dffad78784ae52aa7c652f3557c73bf https://doi.org/10.1007/s13258-015-0383-1 |
حقوق: | CLOSED |
رقم الأكسشن: | edsair.doi...........9dffad78784ae52aa7c652f3557c73bf |
قاعدة البيانات: | OpenAIRE |
تدمد: | 20929293 19769571 |
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