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Volume 20
Issue 9
10.3390/ijms20092200
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Article

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

by
Mikhail V. Trostnikov
1,2,
Natalia V. Roshina
1,2,
Stepan V. Boldyrev
1,2,
Ekaterina R. Veselkina
1,
Andrey A. Zhuikov
1,
Anna V. Krementsova
1,3 and
Elena G. Pasyukova
1,*
1
Institute of Molecular Genetics of RAS, Kurchatov Sq. 2, 123182 Moscow, Russia
2
Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkin 3, 119991 Moscow, Russia
3
Emmanuel Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, 119334 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2200; https://doi.org/10.3390/ijms20092200
Received: 30 March 2019 / Revised: 30 April 2019 / Accepted: 2 May 2019 / Published: 4 May 2019
(This article belongs to the Special Issue Aging and Age-related Disorders: From Molecular Mechanisms to Therapies)
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Abstract

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. View Full-Text
Keywords: GSK3 (glycogen synthase kinase 3); protein kinases; transcription; lifespan; the nervous system; Drosophila melanogaster GSK3 (glycogen synthase kinase 3); protein kinases; transcription; lifespan; the nervous system; Drosophila melanogaster
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MDPI and ACS Style

Trostnikov, M.V.; Roshina, N.V.; Boldyrev, S.V.; Veselkina, E.R.; Zhuikov, A.A.; Krementsova, A.V.; Pasyukova, E.G. 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. Int. J. Mol. Sci. 2019, 20, 2200. https://doi.org/10.3390/ijms20092200

AMA Style

Trostnikov MV, Roshina NV, Boldyrev SV, Veselkina ER, Zhuikov AA, Krementsova AV, Pasyukova EG. 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. International Journal of Molecular Sciences. 2019; 20(9):2200. https://doi.org/10.3390/ijms20092200

Chicago/Turabian Style

Trostnikov, Mikhail V., Natalia V. Roshina, Stepan V. Boldyrev, Ekaterina R. Veselkina, Andrey A. Zhuikov, Anna V. Krementsova, and Elena G. Pasyukova. 2019. "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" International Journal of Molecular Sciences 20, no. 9: 2200. https://doi.org/10.3390/ijms20092200

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