囊泡运输-中国细胞生物学学会.pptVIP

囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 囊泡运输缺陷相关的人类疾病 Gareth J. Howell et. al. 2006, International Review of Cytology 诺奖的启示 科学传承—站在前人的肩膀上 重要科学问题—敏锐的洞察力 扎实的训练—名师与殿堂 科学氛围—团队和领袖 科学的方法论—简单、精美而高效的研究系统 多年的坚持—兴趣是驱动力 科学规划与自由探索 * Plasmalemmal precursor vesicles (PPVs) during early neurite elongation Pfenninger KH 2009 Nature Reviews Neuroscience 研究背景:轴突发育需要细胞膜的极性插入 * Wang T., Liu Y., et al. Dev. Cell 2011, 21: 431 Both Lgl1 and Rab10 are required for axon development Lgl1 promotes axon development through Rab10 Lgl1 promotes membrane localization of Rab10 by releasing Rab10 from GDI Lgl1-Rab10 system promotes directional membrane insertion during axon development 发现轴突发育细胞膜转运机制： --抑癌蛋白Lgl1通过激活Rab10促进细胞膜的极性插入 --Rab10是PPV的标志分子 * Paramagnetic beads coated with purified Lgl1 protein were incubated with cortical neuron postnuclear supernatant Identity of Lgl1-associated vesicle Negative: Rab5 (early endosome) Rab11 (recycling endosome) VAMP2 (synaptic vesicle) Bip (Endoplasmic Reticulum) Positive: Rab10 TGN38 (trans-golgi network) TrkB, Frizzled7, IGFR (growth factor receptors) Dvl, Par3, Par6, aPKC (polarity proteins) PPV的特征和分子组成 Wang T., et al Dev. Cell 2011 * 关于PPV发生 Hirokawa N et al Neuron 2010 发现Myosin Vb在Rab10-PPV从TGN fission过程中起关键作用, 改变了以前Myosin主要负责物质运输的认识。 Control siMyosinVb * Ath5-mcherry fish 2dpf Retinal ganglion cells as a model to study axon development By Yang Liu * TAT-exon D injection causes loss of optic nerves Liu Y., et al Nat. Commun. 2013 * PPV如何形成？ PPV如何沿着轴突运输