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Role of SIK family in the regulation of sleep/wakefulness

Research Project

Project/Area Number 17H04023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Environmental physiology(including physical medicine and nutritional physiology)
Research InstitutionUniversity of Tsukuba

Principal Investigator

Funato Hiromasa  筑波大学, 国際統合睡眠医科学研究機構, 客員教授 (90363118)

Co-Investigator(Kenkyū-buntansha) 三好 千香  筑波大学, 国際統合睡眠医科学研究機構, 助教 (60613437)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords睡眠覚醒 / キナーゼ / 細胞内シグナル / 遺伝子改変マウス / リン酸化酵素 / CRISPR / ゲノム編集
Outline of Final Research Achievements

We investigated the role of SIK1(S577) and SIK2(S587), PKA-phosphorylated serines of SIK1 and SIK2, in sleep regulation. Sik1(S577A) mice had shorter wake time, longer NREMS time, and higher NREMS delta density than wild-type mice. Sik2( S587A) mice showed increased NREMS delta power. Sik1(S577A) mice showed normal circadian behavior. Sik2(S587A) mice showed weight gain comparable to wild-type mice, although Sik2 is expressed predominantly in brown adipose tissue. These results indicate that PKA-SIK signaling is involved in the regulation of the need for sleep.

Academic Significance and Societal Importance of the Research Achievements

睡眠制御がSIKファミリーに共通した役割であることは、SIKファミリーに共通した上流及び下流シグナルが睡眠必要量の決定を担うことを示している。SIK1は概日リズム行動に、SIK2は褐色脂肪組織を場とするエネルギー代謝に関与するという報告があるもの、今回の検討では変化が見られなかった。SIKファミリーのキナーゼ活性はLKB1が制御していることから、PKAによる制御は特定の機能や行動に限定されると考えられる。
睡眠制御機構の理解が深まれば睡眠障害、気分障害等の疾患の介入方法開発を可能にする。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (35 results)

All 2020 2019 2018 2017 Other

All Journal Article (17 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 17 results,  Open Access: 17 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 10 results) Book (1 results) Remarks (5 results)

  • [Journal Article] Forward genetic approach for behavioral neuroscience using animal models2020

    • Author(s)
      Hiromasa Funato
    • Journal Title

      Proceedings of the Japan Academy, Series B

      Volume: 96 Issue: 1 Pages: 10-31

    • DOI

      10.2183/pjab.96.002

    • NAID

      130007783761

    • ISSN
      0386-2208, 1349-2896
    • Year and Date
      2020-01-10
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of using smartphone during breast-feeding2019

    • Author(s)
      Nakagawa Haruka、Yoshida Sachine、Ohnishi Ayumi、Terada Tsutomu、Funato Hiromasa、Tsukamoto Masahiko
    • Journal Title

      UbiComp/ISWC '19 Adjunct: Adjunct Proc 2019 ACM Int Joint Conf Pervasive and Ubiquit Comput and Proc 2019 ACM Int Symp Wearable Comput

      Volume: - Pages: 1190-1193

    • DOI

      10.1145/3341162.3344840

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MC-SleepNet: Large-scale Sleep Stage Scoring in Mice by Deep Neural Networks.2019

    • Author(s)
      Yamabe M, Horie K, Shiokawa H, Funato H, Yanagisawa M, Kitagawa H.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 15793-15793

    • DOI

      10.1038/s41598-019-51269-8

    • NAID

      120007127675

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential Roles of Each Orexin Receptor Signaling in Obesity2019

    • Author(s)
      Kakizaki Miyo、Tsuneoka Yousuke、Takase Kenkichi、Kim Staci J.、Choi Jinhwan、Ikkyu Aya、Abe Manabu、Sakimura Kenji、Yanagisawa Masashi、Funato Hiromasa
    • Journal Title

      iScience

      Volume: 20 Pages: 1-13

    • DOI

      10.1016/j.isci.2019.09.003

    • NAID

      120007132695

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain.2019

    • Author(s)
      Furuse T, Mizuma H, Hirose Y, Kushida T, Yamada I, Miura I, Masuya H, Funato H, Yanagisawa M, Onoe H, Wakana S.
    • Journal Title

      Dis Model Mech.

      Volume: 12 Issue: 9 Pages: 38828-38828

    • DOI

      10.1242/dmm.038828

    • NAID

      120007161317

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Methodology and theoretical basis of forward genetic screening for sleep/wakefulness in mice.2019

    • Author(s)
      Miyoshi C, Kim SJ, Ezaki T, Ikkyu A, Hotta-Hirashima N, Kanno S, Kakizaki M, Yamada M, Wakana S, Yanagisawa M, Funato H
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 116 Issue: 32 Pages: 16062-16067

    • DOI

      10.1073/pnas.1906774116

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice2018

    • Author(s)
      Honda Takato、Fujiyama Tomoyuki、Miyoshi Chika、Ikkyu Aya、Hotta-Hirashima Noriko、Kanno Satomi、Mizuno Seiya、Sugiyama Fumihiro、Takahashi Satoru、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 41 Pages: 10458-10463

    • DOI

      10.1073/pnas.1810823115

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response2018

    • Author(s)
      Iwasaki Kanako、Komiya Haruna、Kakizaki Miyo、Miyoshi Chika、Abe Manabu、Sakimura Kenji、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 12 Pages: 535-535

    • DOI

      10.3389/fnins.2018.00535

    • NAID

      120007133025

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of sleep deprivation-induced hepatic steatosis and insulin resistance in mice2018

    • Author(s)
      Shigiyama F, Kumashiro N, Tsuneoka Y, Igarashi H, Yoshikawa F, Kakehi S, Funato H, Hirose T
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 315 Issue: 5 Pages: E848-E858

    • DOI

      10.1152/ajpendo.00072.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Corticotropin-Releasing Factor Receptor 1 in the Anterior Cingulate Cortex Mediates Maternal Absence-Induced Attenuation of Transport Response in Mouse Pups2018

    • Author(s)
      Yoshida Sachine、Ohnishi Ryuko、Tsuneoka Yousuke、Yamamoto-Mimura Yuka、Muramatsu Reiko、Kato Tadafumi、Funato Hiromasa、Kuroda Kumi O.
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 12 Pages: 1-14

    • DOI

      10.3389/fncel.2018.00204

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain2018

    • Author(s)
      Fujiyama Tomoyuki、Miyashita Satoshi、Tsuneoka Yousuke、Kanemaru Kazumasa、Kakizaki Miyo、Kanno Satomi、Ishikawa Yukiko、Yamashita Mariko、Owa Tomoo、Nagaoka Mai、Kawaguchi Yoshiya、Yanagawa Yuchio、Magnuson Mark A.、Muratani Masafumi、Shibuya Akira、Nabeshima Yo-ichi、Yanagisawa Masashi、Funato Hiromasa、Hoshino Mikio
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 1 Pages: 79-94

    • DOI

      10.1016/j.celrep.2018.06.010

    • NAID

      120006491717

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative phosphoproteomic analysis of the molecular substrates of sleep need2018

    • Author(s)
      Z. Wang, J. Ma, C. Miyoshi, Y. Li, M Sato, Y. Ogawa, T. Lou, C. Ma, X. Gao, C. Lee, T. Fujiyama, X. Yang, S. Zhou, N. Hotta-Hirashima, D. Klewe-Nebenus, A. Ikkyu, M. Kakizaki, S. Kanno, L. Cao, S. Takahashi, J. Peng, Y. Yu, H. Funato, M. Yanagisawa, Q. Liu
    • Journal Title

      Nature

      Volume: 558 Issue: 7710 Pages: 435-439

    • DOI

      10.1038/s41586-018-0218-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors2018

    • Author(s)
      Wang, Y., Cao, L., Lee, C-Y., Matsuo, M., Wu, K., Asher, G., Saitoh, T., Klewe-Nebenius, D., Wang, L., Soya, S., Hasegawa, E., Cherasse, Y., Miyoshi,C., Irukayama, Y., Wang, Z., Sakurai, K., Funato, H., Sakurai, T., Yanagisawa, M., Nagase, H., Kobayakawa, R., Kobayakawa, K., Beutler, B., Liu, Q
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2041-2041

    • DOI

      10.1038/s41467-018-04324-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunolocalization of muscarinic M1 receptor in the rat medial prefrontal cortex2018

    • Author(s)
      Oda Satoko、Tsuneoka Yousuke、Yoshida Sachine、Adachi-Akahane Satomi、Ito Masanori、Kuroda Masaru、Funato Hiromasa
    • Journal Title

      Journal of Comparative Neurology

      Volume: 526 Issue: 8 Pages: 1329-1350

    • DOI

      10.1002/cne.24409

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sleep/Wake Behaviors in Mice During Pregnancy and Pregnancy-Associated Hypertensive Mice2017

    • Author(s)
      Komiya Haruna、Miyoshi Chika、Iwasaki Kanako、Hotta-Hirashima Noriko、Ikkyu Aya、Kanno Satomi、Honda Takato、Gosho Masahiko、Hamada Hiromi、Satoh Toyomi、Fukamizu Akiyoshi、Funato Hiromasa、Yanagisawa Masashi
    • Journal Title

      Sleep

      Volume: 41 Issue: 3 Pages: 1-1

    • DOI

      10.1093/sleep/zsx209

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neurotransmitters and neuropeptides in gonadal steroid receptor-expressing cells in medial preoptic area subregions of the male mouse2017

    • Author(s)
      Yousuke Tsuneoka, Sachine Yoshida, Kenkichi Takase, Satoko Oda, Masaru Kuroda, Hiromasa Funato
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41598-017-10213-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Moxd1 Is a Marker for Sexual Dimorphism in the Medial Preoptic Area, Bed Nucleus of the Stria Terminalis and Medial Amygdala2017

    • Author(s)
      Tsuneoka Y and Funato H et al.
    • Journal Title

      Front Neuroanat

      Volume: 11 Pages: 26-26

    • DOI

      10.3389/fnana.2017.00026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] SIK family regulates sleep/wakefulness in mice2020

    • Author(s)
      Hiromasa Funato
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 睡眠覚醒の謎に挑む2019

    • Author(s)
      船戸弘正
    • Organizer
      第8回日本食品分析センター技術成果発表会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] SIKファミリーによる睡眠覚醒とエネルギー代謝制御2019

    • Author(s)
      船戸弘正
    • Organizer
      第92回日本生化学学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Forward genetics in mice identified novel sleep-regulating genes2019

    • Author(s)
      Hiromasa Funato
    • Organizer
      V World Congress of Chronobiology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Sleep and energy metabolism regulation though mouse genetics2019

    • Author(s)
      Hiromasa Funato
    • Organizer
      CIBR Beijing Conference on Brain & Behavior
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Altered sleep/wakefulness behavior and phosphoproteomics in Sik3 mutant mice2018

    • Author(s)
      Hiromasa Funato
    • Organizer
      第41回日本分子生物学会年会 シンポジウム "個体行動制御の細胞内シグナル" \
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Forward genetic research on sleep using mice2018

    • Author(s)
      Hiromasa Funato
    • Organizer
      第41回日本神経科学大会 シンポジウム "サーカディアンリズムと睡眠を制御する神経機構"
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] マウスを用いたフォワード・ジェネティクス研究による新規睡眠制御分子同定2018

    • Author(s)
      船戸弘正
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 視索前野の性差とその発生2018

    • Author(s)
      船戸弘正
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Forward genetic analysis of sleep in mice2018

    • Author(s)
      Hiromasa Funato
    • Organizer
      Gordon Research Conference "Sleep Regulation and Function"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Forward genetic analysis of sleep in mice2018

    • Author(s)
      Hiromasa Funato, Masashi Yanagisawa
    • Organizer
      Keystone symposia "State of the Brain"
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウスを用いた睡眠のフォワード・ジェネティクス研究2017

    • Author(s)
      船戸弘正
    • Organizer
      第24回日本時間生物学会学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Book] ブレインサイエンスレビュー2020 新規睡眠制御分子同定による睡眠覚醒機構の解明を目指して(269-288)2020

    • Author(s)
      船戸弘正
    • Total Pages
      344
    • Publisher
      クバプロ
    • ISBN
      9784878051609
    • Related Report
      2019 Annual Research Report
  • [Remarks] 国際統合睡眠医科学研究機構柳沢・船戸研究室

    • URL

      http://sleepymouse.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東邦大学医学部解剖学講座

    • URL

      http://toho-funatolab.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 筑波大学IIIS Y-F lab

    • URL

      http://sleepymouse.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] http://sleepymouse.jp/

    • Related Report
      2017 Annual Research Report
  • [Remarks] http://toho-funatolab.jp/

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2022-01-27  

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