A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila
Sleep behavior has been observed from non-vertebrates to humans. Sleepy mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the salt-inducible kinase 3 (Sik3) gene, conserved among animals. The skipped exon includes a serine residue that is pho...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1181555/full |
| _version_ | 1797741481262317568 |
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| author | Riho Kobayashi Shin Nakane Jun Tomita Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Kazuhiko Kume |
| author_facet | Riho Kobayashi Shin Nakane Jun Tomita Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Kazuhiko Kume |
| author_sort | Riho Kobayashi |
| collection | DOAJ |
| description | Sleep behavior has been observed from non-vertebrates to humans. Sleepy mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the salt-inducible kinase 3 (Sik3) gene, conserved among animals. The skipped exon includes a serine residue that is phosphorylated by protein kinase A. Overexpression of a mutant gene with the conversion of this serine into alanine (Sik3-SA) increased sleep in both mice and the fruit fly Drosophila melanogaster. However, the mechanism by which Sik3-SA increases sleep remains unclear. Here, we found that Sik3-SA overexpression in all neurons increased sleep under both light–dark (LD) conditions and constant dark (DD) conditions in Drosophila. Additionally, overexpression of Sik3-SA only in PDF neurons, which are a cluster of clock neurons regulating the circadian rhythm, increased sleep during subjective daytime while decreasing the amplitude of circadian rhythm. Furthermore, suppressing Sik3-SA overexpression specifically in PDF neurons in flies overexpressing Sik3-SA in all neurons reversed the sleep increase during subjective daytime. These results indicate that Sik3-SA alters the circadian function of PDF neurons and leads to an increase in sleep during subjective daytime under constant dark conditions. |
| first_indexed | 2024-03-12T14:27:58Z |
| format | Article |
| id | doaj.art-08d35c71955a46749f1dfe995f1b1cfa |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-03-12T14:27:58Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-08d35c71955a46749f1dfe995f1b1cfa2023-08-17T23:25:34ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-08-011710.3389/fnins.2023.11815551181555A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in DrosophilaRiho Kobayashi0Shin Nakane1Jun Tomita2Hiromasa Funato3Hiromasa Funato4Masashi Yanagisawa5Kazuhiko Kume6Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanSchool of Medicine, Toho University, Tokyo, JapanInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, JapanDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, JapanSleep behavior has been observed from non-vertebrates to humans. Sleepy mutation in mice resulted in a notable increase in sleep and was identified as an exon-skipping mutation of the salt-inducible kinase 3 (Sik3) gene, conserved among animals. The skipped exon includes a serine residue that is phosphorylated by protein kinase A. Overexpression of a mutant gene with the conversion of this serine into alanine (Sik3-SA) increased sleep in both mice and the fruit fly Drosophila melanogaster. However, the mechanism by which Sik3-SA increases sleep remains unclear. Here, we found that Sik3-SA overexpression in all neurons increased sleep under both light–dark (LD) conditions and constant dark (DD) conditions in Drosophila. Additionally, overexpression of Sik3-SA only in PDF neurons, which are a cluster of clock neurons regulating the circadian rhythm, increased sleep during subjective daytime while decreasing the amplitude of circadian rhythm. Furthermore, suppressing Sik3-SA overexpression specifically in PDF neurons in flies overexpressing Sik3-SA in all neurons reversed the sleep increase during subjective daytime. These results indicate that Sik3-SA alters the circadian function of PDF neurons and leads to an increase in sleep during subjective daytime under constant dark conditions.https://www.frontiersin.org/articles/10.3389/fnins.2023.1181555/fullsleepPDFSik3circadian rhythmDrosophila |
| spellingShingle | Riho Kobayashi Shin Nakane Jun Tomita Hiromasa Funato Hiromasa Funato Masashi Yanagisawa Kazuhiko Kume A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila Frontiers in Neuroscience sleep Sik3 circadian rhythm Drosophila |
| title | A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila |
| title_full | A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila |
| title_fullStr | A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila |
| title_full_unstemmed | A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila |
| title_short | A phosphorylation-deficient mutant of Sik3, a homolog of Sleepy, alters circadian sleep regulation by PDF neurons in Drosophila |
| title_sort | phosphorylation deficient mutant of sik3 a homolog of sleepy alters circadian sleep regulation by pdf neurons in drosophila |
| topic | sleep Sik3 circadian rhythm Drosophila |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1181555/full |
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