Quantitative interaction proteomics of neurodegenerative disease proteins.
Quantitative interaction proteomics of neurodegenerative disease proteins.
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DOI：
10.1016/j.celrep.2015.04.030
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发表时间：
2015-05-19
期刊：
影响因子：
8.8
通讯作者：
Selbach, Matthias
中科院分区：
文献类型：
--
作者：
Hosp, Fabian;Vossfeldt, Hannes;Heinig, Matthias;Vasiljevic, Djordje;Arumughan, Anup;Wyler, Emanuel;Landthaler, Markus;Hubner, Norbert;Wanker, Erich E.;Lannfelt, Lars;Ingelsson, Martin;Lalowski, Maciej;Voigt, Aaron;Selbach, Matthias
一些蛋白质与神经退行性疾病（NDD）有关，但它们的分子功能尚未完全了解。在这里，我们使用定量相互作用蛋白质组学来鉴定淀粉样蛋白β前体蛋白（APP）和早老素-1（PSEN 1）与阿尔茨海默病（AD）、亨廷顿蛋白（HTT）与亨廷顿病、帕金蛋白（PARK 2）与帕金森病以及共济失调蛋白-1（ATXN 1）与脊髓小脑性共济失调1型的结合伴侣。我们的网络揭示了蛋白质降解和错误折叠的共同特征，并概括了已知的生物学。毒性修饰剂筛选和与全基因组关联研究的比较表明，相互作用伴侣与体内疾病表型显著相关。直接比较野生型蛋白和疾病相关的变异体，确定了参与发病机制的结合剂，突出了差异相互作用组作图的价值。最后，我们表明，线粒体蛋白LRPPRC相互作用优先与早发性AD的APP的变体。这种相互作用似乎诱导线粒体功能障碍，这是AD的早期表型。Hosp等人表明，神经退行性疾病蛋白质的定量相互作用蛋白质组学捕获了与发病机制相关的相互作用。差异相互作用组作图揭示了线粒体蛋白LRPPRC与早发性阿尔茨海默病（AD）APP变体的优先结合，可能导致AD中观察到的线粒体功能障碍。
Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer’s disease (AD), Huntingtin (HTT) for Huntington’s disease, Parkin (PARK2) for Parkinson’s disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD. Hosp et al. show that quantitative interaction proteomics of neurodegenerative disease proteins captures interactions relevant to pathogenesis. Differential interactome mapping reveals preferential binding of the mitochondrial protein LRPPRC with an early-onset Alzheimer’s disease (AD) variant of APP, potentially contributing to mitochondrial dysfunction observed in AD.
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DOI：
10.1016/j.bbadis.2009.07.007
发表时间：
2010-01
影响因子：
6.2
作者：
Devi, Latha;Anandatheerthavarada, Hindupur K.
通讯作者：
Anandatheerthavarada, Hindupur K.
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Harold, Denise;Abraham, Richard;Hollingworth, Paul;Sims, Rebecca;Gerrish, Amy;Hamshere, Marian L.;Pahwa, Jaspreet Singh;Moskvina, Valentina;Dowzell, Kimberley;Williams, Amy;Jones, Nicola;Thomas, Charlene;Stretton, Alexandra;Morgan, Angharad R.;Lovestone, Simon;Powell, John;Proitsi, Petroula;Lupton, Michelle K.;Brayne, Carol;Rubinsztein, David C.;Gill, Michael;Lawlor, Brian;Lynch, Aoibhinn;Morgan, Kevin;Brown, Kristelle S.;Passmore, Peter A.;Craig, David;McGuinness, Bernadette;Todd, Stephen;Holmes, Clive;Mann, David;Smith, A. David;Love, Seth;Kehoe, Patrick G.;Hardy, John;Mead, Simon;Fox, Nick;Rossor, Martin;Collinge, John;Maier, Wolfgang;Jessen, Frank;Schuermann, Britta;van den Bussche, Hendrik;Heuser, Isabella;Kornhuber, Johannes;Wiltfang, Jens;Dichgans, Martin;Froelich, Lutz;Hampel, Harald;Huell, Michael;Rujescu, Dan;Goate, Alison M.;Kauwe, John S. K.;Cruchaga, Carlos;Nowotny, Petra;Morris, John C.;Mayo, Kevin;Sleegers, Kristel;Bettens, Karolien;Engelborghs, Sebastiaan;De Deyn, Peter P.;Van Broeckhoven, Christine;Livingston, Gill;Bass, Nicholas J.;Gurling, Hugh;McQuillin, Andrew;Gwilliam, Rhian;Deloukas, Panagiotis;Al-Chalabi, Ammar;Shaw, Christopher E.;Tsolaki, Magda;Singleton, Andrew B.;Guerreiro, Rita;Muehleisen, Thomas W.;Noethen, Markus M.;Moebus, Susanne;Joeckel, Karl-Heinz;Klopp, Norman;Wichmann, H-Erich;Carrasquillo, Minerva M.;Pankratz, V. Shane;Younkin, Steven G.;Holmans, Peter A.;O'Donovan, Michael;Owen, Michael J.;Williams, Julie
通讯作者：
Williams, Julie
影响因子：
12.4
作者：
Hirabayashi, M;Inoue, K;Kakizuka, A
通讯作者：
Kakizuka, A
影响因子：
3.5
作者：
Choi, Jung Young;Ryu, Jeong Hee;Lee, Do Hee
通讯作者：
Lee, Do Hee