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突起伸展・回路形成 2
Axonal/Dendritic Growth and Circuit Formation 2

開催日 2014/9/13
時間 16:00 - 17:00
会場 Room J(313+314)
Chairperson(s) 竹居 光太郎 / Kohtaro Takei (横浜市立大学大学院生命医科学研究科 / Graduate School of Medicine, Life Science, Yokohama City University, Japan)
生沼 泉 / Izumi Oinuma (京都大学大学院生命科学研究科生体システム学 / Laboratory of Molecular Neurobiology, Garduate School of Biostudies, Kyoto University, Japan)

Dogi serves as a platform for early endosome organization during axon elongation

  • O3-J-4-3
  • 佐久間 知佐子 / Chisako Sakuma:1 川内 健史 / Takeshi Kawauchi:2,3 原口 朱夏 / Shuka Haraguchi:1 鹿内 弥磨 / Mima Shikanai:2 山口 良文 / Yoshifumi Yamaguchi:1,3 Gelfand Vladimir I / Vladimir I Gelfand:5 Luo Liqun / Liqun Luo:6 三浦 正幸 / Masayuki Miura:1,4 千原 崇裕 / Takahiro Chihara:1,3,4 
  • 1:東大・院薬・遺伝 / Dept. Genetics, Grad. Sch. of Pharm. Sci., Univ. of Tokyo, Japan 2:慶應大・医・生理 / Dept. Physiol., Keio Univ. Sch. of Med., Japan 3:PRESTO, JST / PRESTO, JST, Japan 4:CREST, JST / CREST, JST, Japan 5:Dept. of Cell. Mol. Biol., Northwestern Univ. Feinberg Sch. of Med., Chicago, U.S.A. / Dept. of Cell. Mol. Biol., Northwestern Univ. Feinberg Sch. of Med., Chicago, U.S.A. 6:HHMI and Dept. of Biol., Stanford Univ. U.S.A. / HHMI and Dept. of Biol., Stanford Univ. U.S.A. 

In developing neurons, endosomal trafficking is crucial to regulate the number and activity of cell-surface molecules at the neurite termini in time and space to respond continuously changing surrounding environment. Especially, early endosomes are essential for cell signalling, serving both as signalling centers and as sorting centers to degrade or recycle cargoes. The organization of early endosomes consists of three steps; endocytosis, clustering, and fusion. Internalized early endosomes are clustered and then undergo fusion. Rab5 is known to promote early endosomal fusion, but the mechanism linking the transport/clustering steps with Rab5 activity is unclear. From a genetic mosaic screen in Drosophila, we identified an evolutionarily conserved molecule, Doubled glomeruli (Dogi), as a key regulator for axon elongation and dendrite branching. dogi knockdown disturbed the early endosome clustering; Rab5-positive early endosomes became smaller and scattered. Dogi genetically and biochemically interacts with both Glued (the regulator of dynein-dependent transport, the homolog of mammalian p150Glued) and Sprint (the guanine nucleotide exchange factor for Rab5, the homolog of mammalian Rin1), suggesting that Dogi is a molecular link between retrograde transport and Rab5 activation. Overexpression of active form of Rab5 in dogi mutant neurons suppressed the axon elongation defects. Thus, Dogi acts as a molecular platform for the early endosome organization that plays important roles in neuronal morphogenesis.

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