新细胞信号传递衔接蛋白现身

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作者：Joel B. Dacks 来源：《PLoS生物学》 发布时间：2011-10-145 M" w8 N: q6 s7 D- e0 O8 y

2 q& q5 _! j. R5 S# l9 g据美国物理学家组织网10月12日（北京时间）报道，学界长期认为，4个衔接蛋白（adaptin）参与了细胞内外以及周围信息的整合与传递。但现在，科学家们找到了第5个衔接蛋白。这一发现将修改教科书并改变细胞生物学研究的面貌。研究发表在10月11日出版的《科学公共图书馆—生物学》上。
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每个非细菌细胞内都有一个“膜贩运系统”，理解该系统如何工作非常重要。与这一系统有关的基因变异可能导致包括阿尔茨海默症、亨廷顿舞蹈症，以及肌萎缩侧索硬化症等在内的神经退行性疾病。% e' G4 H+ H% H
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此前科学家们认为，4个衔接蛋白在其中起关键作用。衔接蛋白以胞膜结合蛋白和胞质蛋白两种形式参与信号转导中蛋白质与蛋白质间的反应，其可为大分子复合物的形成提供支架，参与胞内信号的整合与传递。/ X1 e& r# |  S* x
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但在最新研究中，加拿大阿尔伯塔大学医学与牙科学院细胞生物学系的乔尔·戴克斯和英国剑桥大学医学研究所的玛格丽特·鲁宾逊携手发现了第5种衔接蛋白。他们认为，这种衔接蛋白已存在数十亿年，只是一直没有被人找到而已。
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戴克斯在一种无害的土壤变形虫内发现了这种衔接蛋白。他意识到，人体细胞内也可能存在同样的蛋白。因此，他与同事鲁宾逊一起，历时3年彻底分析了新发现衔接蛋白的生物学性质。' H4 E- k) y  M  ?: K" [" G+ `

/ {' A+ e$ F8 V( u戴克斯说：“我们已经知道，这种衔接蛋白与另外一种神经系统退行性变性疾病——遗传性痉挛性截瘫有关。”他表示，“膜贩运系统”这种机制非常普遍，不仅存在于人体细胞中，也出现在植物、寄生虫和海藻体内，这意味着，它不仅是各种细胞的一种普遍特征，而且也相当古老，对第五种衔接蛋白了解得越多，就越能知道细胞刚开始组建时发生了什么事情。
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最新研究很可能会改变许多细胞生物学家的研究。戴克斯说：“科学家们需要理解细胞的基本图谱才能知道它为何会出错，现在，我们在该图谱上发现了以前没有找到的关键因素。它将为细胞生物学打开一个全新的研究领域。”他表示，接下来的工作是将实验室发现的理论整合起来，并提出更好的与细胞进化有关的理论。（来源：科技日报 刘霞）
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" R& }) k) d+ T' C4 CThe Fifth Adaptor Protein Complex
/ U% z4 ~+ {  M! T! lAdaptor protein (AP) complexes facilitate the trafficking of cargo from one membrane compartment of the cell to another by recruiting other proteins to particular types of vesicles. For over 10 years, it has been assumed that there are four, and only four, distinct AP complexes in eukaryotic cells. We report the existence of a fifth AP complex, AP-5. Immunolocalisation and RNAi knockdown experiments both indicate that AP-5 is involved in trafficking proteins from endosomes towards other membranous compartments. There are genetic links between AP-5 and hereditary spastic paraplegia, a group of human genetic disorders characterised by progressive spasticity in the lower limbs. Phylogenetic analyses indicate that AP-5 was already present in the last eukaryotic common ancestor over a billion years ago.
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8 C9 t- {4 `8 {3 RJennifer Hirst1, Lael D. Barlow2, Gabriel Casey Francisco2, Daniela A. Sahlender1, Matthew N. J. Seaman1, Joel B. Dacks2*, Margaret S. Robinson1*
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1 g, W1 D) |  ?6 t1 University of Cambridge, Cambridge Institute for Medical Research, Cambridge, United Kingdom, 2 Department of Cell Biology, University of Alberta, Edmonton, Canada
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7 _/ S  o# s; v* K' GAbstract Top
8 _9 Y% p( j9 k9 \5 ~Adaptor protein (AP) complexes sort cargo into vesicles for transport from one membrane compartment of the cell to another. Four distinct AP complexes have been identified, which are present in most eukaryotes. We report the existence of a fifth AP complex, AP-5. Tagged AP-5 localises to a late endosomal compartment in HeLa cells. AP-5 does not associate with clathrin and is insensitive to brefeldin A. Knocking down AP-5 subunits interferes with the trafficking of the cation-independent mannose 6-phosphate receptor and causes the cell to form swollen endosomal structures with emanating tubules. AP-5 subunits can be found in all five eukaryotic supergroups, but they have been co-ordinately lost in many organisms. Concatenated phylogenetic analysis provides robust resolution, for the first time, into the evolutionary order of emergence of the adaptor subunit families, showing AP-3 as the basal complex, followed by AP-5, AP-4, and AP-1 and AP-2. Thus, AP-5 is an evolutionarily ancient complex, which is involved in endosomal sorting, and which has links with hereditary spastic paraplegia.1 N  n3 y6 L* S& W2 u
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Author Summary Top
; v. Z5 ~) C3 p" N% \2 g+ DAdaptor protein (AP) complexes facilitate the trafficking of cargo from one membrane compartment of the cell to another by recruiting other proteins to particular types of vesicles. For over 10 years, it has been assumed that there are four, and only four, distinct AP complexes in eukaryotic cells. We report the existence of a fifth AP complex, AP-5. Immunolocalisation and RNAi knockdown experiments both indicate that AP-5 is involved in trafficking proteins from endosomes towards other membranous compartments. There are genetic links between AP-5 and hereditary spastic paraplegia, a group of human genetic disorders characterised by progressive spasticity in the lower limbs. Phylogenetic analyses indicate that AP-5 was already present in the last eukaryotic common ancestor over a billion years ago.
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. W8 {  c. i! ~, c" Z) Hhttp://www.plosbiology.org/artic ... ournal.pbio.1001170

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