Disordered Expression of shaggy , the Drosophila Gene Encoding a Serine-Threonine Protein Kinase GSK3, Affects the Lifespan in a Transcript-, Stage-, and Tissue-Specific Manner.

Autor: Trostnikov MV; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. mikhail.trostnikov@gmail.com.; Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkin 3, Moscow 119991, Russia. mikhail.trostnikov@gmail.com., Roshina NV; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. nwumr@yandex.ru.; Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkin 3, Moscow 119991, Russia. nwumr@yandex.ru., Boldyrev SV; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. beibaraban34@gmail.com.; Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkin 3, Moscow 119991, Russia. beibaraban34@gmail.com., Veselkina ER; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. veselkinaer@gmail.com., Zhuikov AA; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. homkabrut@gmail.com., Krementsova AV; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. akrementsova@mail.ru.; Emmanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, 119334, Moscow, Russia. akrementsova@mail.ru., Pasyukova EG; Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182, Moscow, Russia. egpas@rambler.ru.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2019 May 04; Vol. 20 (9). Date of Electronic Publication: 2019 May 04.
DOI: 10.3390/ijms20092200
Abstrakt: GSK3 (glycogen synthase kinase 3) is a conserved protein kinase governing numerous regulatory pathways. In Drosophila melanogaster , GSK3 is encoded by shaggy ( sgg ), which forms 17 annotated transcripts corresponding to 10 protein isoforms. Our goal was to demonstrate how differential sgg transcription affects lifespan, which GSK3 isoforms are important for the nervous system, and which changes in the nervous system accompany accelerated aging. Overexpression of three sgg transcripts affected the lifespan in a stage- and tissue-specific way: sgg-RA and sgg-RO affected the lifespan only when overexpressed in muscles and in embryos, respectively; the essential sgg-RB transcript affected lifespan when overexpressed in all tissues tested. In the nervous system, only sgg-RB overexpression affected lifespan, causing accelerated aging in a neuron-specific way, with the strongest effects in dopaminergic neurons and the weakest effects in GABAergic neurons. Pan-neuronal sgg - RB overexpression violated the properties of the nervous system, including the integrity of neuron bodies; the number, distribution, and structure of mitochondria; cytoskeletal characteristics; and synaptic activity. Such changes observed in young individuals indicated premature aging of their nervous system, which paralleled a decline in survival. Our findings demonstrated the key role of GSK3 in ensuring the link between the pathology of neurons and lifespan.
Competing Interests: The authors declare no conflict of interest.
Databáze: MEDLINE
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