The fifth adaptor protein complex.
The fifth adaptor protein complex.
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DOI：
10.1371/journal.pbio.1001170
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发表时间：
2011-10
期刊：
影响因子：
9.8
通讯作者：
Robinson MS
中科院分区：
文献类型：
--
作者：
Hirst J;Barlow LD;Francisco GC;Sahlender DA;Seaman MN;Dacks JB;Robinson MS
衔接蛋白 (AP) 复合物将货物分类到囊泡中，以便从细胞的一个膜室运输到另一个膜室。已鉴定出四种不同的 AP 复合物，它们存在于大多数真核生物中。我们报告了第五种 AP 复合物的存在，即 AP-5。标记的 AP-5 定位于 HeLa 细胞的晚期内体区室。 AP-5 不与网格蛋白结合，并且对布雷菲德菌素 A 不敏感。敲低 AP-5 亚基会干扰不依赖于阳离子的甘露糖 6-磷酸受体的运输，并导致细胞形成带有发散小管的肿胀内体结构。 AP-5 亚基可以在所有五个真核生物超群中找到，但它们在许多生物体中已经同步丢失。串联系统发育分析首次提供了接头亚基家族出现的进化顺序的可靠分辨率，显示 AP-3 为基础复合体，其次是 AP-5、AP-4、AP-1 和 AP-2。因此，AP-5是一种进化上古老的复合体，它参与内体分选，并且与遗传性痉挛性截瘫有关。衔接蛋白 (AP) 复合物通过将其他蛋白质募集到特定类型的囊泡中，促进货物从细胞的一个膜室运输到另一个膜室。十多年来，人们一直假设真核细胞中有四种（而且只有四种）不同的 AP 复合物。我们报告了第五种 AP 复合物的存在，即 AP-5。免疫定位和 RNAi 敲除实验均表明 AP-5 参与将蛋白质从内体运输到其他膜区室。 AP-5 与遗传性痉挛性截瘫之间存在遗传联系，遗传性痉挛性截瘫是一组以下肢进行性痉挛为特征的人类遗传性疾病。系统发育分析表明，AP-5 在十亿多年前就已经存在于最后一个真核生物共同祖先中。
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. Adaptor 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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影响因子：
56.9
作者：
Dell'Angelica, EC;Klumperman, J;Bonifacino, JS
通讯作者：
Bonifacino, JS
DOI：
10.1073/pnas.0707318105
发表时间：
2008-01-15
影响因子：
11.1
作者：
Dacks, Joel B.;Poon, Pak P.;Field, Mark C.
通讯作者：
Field, Mark C.
影响因子：
6.8
作者：
GORBALENYA, AE;KOONIN, EV
通讯作者：
KOONIN, EV
DOI：
10.1038/nrn2946
发表时间：
2011-01
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Blackstone C;O'Kane CJ;Reid E
通讯作者：
Reid E
影响因子：
11.8
作者：
Burgos, Patricia V.;Mardones, Gonzalo A.;Rojas, Adriana L.;daSilva, Luis L. P.;Prabhu, Yogikala;Hurley, James H.;Bonifacino, Juan S.
通讯作者：
Bonifacino, Juan S.