東京大学グローバルCOE『統合生命学』特別セミナー
東京大学 大学院理学系研究科 生物化専攻セミナー
演者:Dr. Kyungjin Kim
Department of Biological Sciences and Brain Research Center for the 21st Century Frontier Program in Neuroscience, Seoul National University, Seoul 151-742, Korea
演題:BioClock: From Molecule to Behavior
日時:平成22年12月13日(月)16:00〜17:30
場所:東京大学理学部3号館4階416号室

Central clock resides in the suprachiamatic nucleus (SCN) of the hypothalamus. Recent studies using genetic and molecular approaches have disclosed fundamental features of molecular circadian clockwork and the network of transcription-translation feedback loops of clock machinery functions not only in the SCN, but also in peripheral clocks in most peripheral tissues. I will discuss our recent findings with two different topics: 1) Adrenal peripheral clock: Adrenal gland has its own intrinsic clock and the peripheral clockwork is tightly linked to steroidogenesis by a StAR(steroidogenic acute regulatory protein). Examination with transgenic mice harboring the adrenal-specific disruption of clock machinery shows that the adrenal clock controls rhythmic StAR expression and glucocorticoid production. The adrenal local clock appears to play an important role in harmonizing circadianphysiology and behavior. 2) Ultradian rhythm of GnRH (Gonadotropin-Releasing Hormone) gene expression: Although pulsatile GnRH secretion from the hypothalamus is reported to be associated with the oscillatory GnRH gene expression, the cellular and molecular mechanism underlying the so-called ‘GnRH pulse generator’ remains to be explored. We generated transgenic mice carrying the rat GnRH promoter-driven destabilized luciferase reporter (GnRH-dsLuc), and monitored the GnRH promoter activity in individual GnRH neurons derived from postnatal hypothalamic slices by using a real-time bioluminescence recording system. GnRH gene expression is quite irregular, but shows robust ultradian oscillation in a cell-intrinsic manner. In vitro administration of kisspeptin, a potent neuropeptide of GnRH neurons amplifies pulsatile GnRH gene expression by augmenting the pulse amplitude. More importantly, rhythmic treatment of the kisspeptin synchronizes the regular oscillatory GnRH gene expression in the hypothalamus.

- Son GH et al. 2008. Adrenal peripheral clock controls the autonomous circadian rhythm of glucocortioid by causing rhythmic steroid production.
PNAS 105:20970-5.
- Lee Y et al. 2010. Coactivation of the CLOCK-BMAL1 complex by CBP mediates resetting of the circadian clock.
J Cell Sci. 123:3547-3557.
- Lee J et al. 2008. Dual modification of BMAL1 by SUMO2/3 and ubiquitin promotes circadian activation of CLOCK/BMAL1 complex.
Mol Cell Biol. 28:6056-65.
- Shim HS et al. 2007. Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock.
EMBO Rep. 8:366-71.
- Kwon I et al. 2006. BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer.
Mol Cell Biol. 26:7318-30.

世話人:理学系研究科 深田 吉孝