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開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

The effect of the active zone protein CAST/ELKS deletion on the structure and function of retinal synapses and visual system

  • P1-037
  • 萩原 明 / Akari Hagiwara:1 阿部 学 / Manabu Abe:2 飛田 耶馬人 / Yamato Hida:1 杉山 直子 / Naoko Sugiyama:1 守矢 敬 / Kei Moriya:1 古川 貴久 / Takahisa Furukawa:3 崎村 健司 / Kenji Sakimura:2 大塚 稔久 / Toshihisa Ohtsuka:1 
  • 1:山梨大 医 生化学第一 / Dept Biochemistry, Faculty of Medicine,University of Yamanashi, Yamanashi, Japan 2:新潟大 脳研究所 細胞神経生物学分野 / Dept Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan 3:大阪大 蛋白質研究所 分子発生学研究室 / Lab Molecular and Developmental Biology, Institute for Protein Research, Osaka University, Osaka, Japan 

Presynaptic active zone is a specialized structure for precise and efficient neurotransmitter release from the nerve terminals, which is known to contain a number of proteins such as CAST/ERC2, ELKS, Piccolo, Bassoon, Munc13-1, and RIMs. Recently we have shown that CAST can be related to the size and function of the rod photoreceptor presynaptic active zones in mouse retina. Here we explored the effect on the deletion of ELKS, a family member of CAST, and the deletion of both CAST and ELKS on the structure of ribbon synapse and the visual processing in retina. Since the null mutant of ELKS was embryonic lethal, we generated a mouse line with conditional gene targeting. The ELKS gene was inactivated with Cre recombinase under the control of the Crx promoter, which is an otx-like homeobox gene expressed abundantly in the photoreceptors. The ELKS conditional knock out (KO) mouse showed normal development and had less effect on the mislocalization of ribbon synapses, which was one of the major phenotypes indicating impaired rod transmitter release in CAST KO. Next we examined CAST and ELKS double knock out (DKO) mice, and found serious body weight reduction in DKO. Inadequate development of DKO seemed to start around 2-3 weeks after the birth, and the body weight at 5-6 weeks reached less than 60% of control (CAST KO) mouse (Cre-/- = 16.0 g, n=6; Cre+/- = 9.5 g, n=3). The morphological analysis with DKO retina revealed regular laminar anatomy from outer nuclear layer (ONL) to ganglion cell layer. However, it showed drastic aberrant synapse formation in the ONL. From these results, we speculate that CAST and ELKS contribute to the maturation of retinal ribbon synapse structurally and functionally.

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