Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration.
Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration.
复制标题
DOI：
10.1016/j.cell.2021.12.041
复制
发表时间：
2022-02-17
期刊：
影响因子：
64.5
通讯作者：
Gan L
中科院分区：
文献类型：
--
作者：
Tracy TE;Madero-Pérez J;Swaney DL;Chang TS;Moritz M;Konrad C;Ward ME;Stevenson E;Hüttenhain R;Kauwe G;Mercedes M;Sweetland-Martin L;Chen X;Mok SA;Wong MY;Telpoukhovskaia M;Min SW;Wang C;Sohn PD;Martin J;Zhou Y;Luo W;Trojanowski JQ;Lee VMY;Gong S;Manfredi G;Coppola G;Krogan NJ;Geschwind DH;Gan L
Tau (MAPT) drives neuronal dysfunction in Alzheimer disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established interactions of Tau with presynaptic vesicle proteins during activity-dependent Tau secretion and mapped the Tau-binding sites to the cytosolic domains of integral synaptic vesicle proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau’s interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multimodal and dynamic Tau interactomes with exquisite spatial resolution shed light on Tau’s role in neuronal function and disease and highlight potential therapeutic targets to block Tau-mediated pathogenesis. By combining APEX and AP-MS proteomic approaches, Tau interactome mapping reveals that Tau interactors are modified by neuronal activity and FTD mutations in human iPSC-derived neurons.
登录
查看更多内容
影响因子：
16.2
作者：
Hoover, Brian R.;Reed, Miranda N.;Su, Jianjun;Penrod, Rachel D.;Kotilinek, Linda A.;Grant, Marianne K.;Pitstick, Rose;Carlson, George A.;Lanier, Lorene M.;Yuan, Li-Lian;Ashe, Karen H.;Liao, Dezhi
通讯作者：
Liao, Dezhi
影响因子：
5.3
作者：
Bardai, Farah H.;Wang, Liqun;Feany, Mel B.
通讯作者：
Feany, Mel B.
影响因子：
4.8
作者：
Biederer, T;Südhof, TC
通讯作者：
Südhof, TC
DOI：
10.1073/pnas.94.1.298
发表时间：
1997-01-07
影响因子：
11.1
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
DOI：
10.1073/pnas.0611318104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Dulubova, Irina;Khvotchev, Mikhail;Rizo, Josep
通讯作者：
Rizo, Josep