期刊
CELL REPORTS
卷 21, 期 3, 页码 679-691出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.09.045
关键词
-
类别
资金
- European Union Seventh Framework Programme [HEALTH-F2-2009-242167, HEALTH-F2-2009-241498]
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BBSRC)
- Medical Research Council (MRC)
- Federation of European Biochemistry Societies postdoctoral fellowship
- Marie Curie FP7-PEOPLE-IEF
- Department of Defense [W81XWH-15-1-0361]
- VIB
- Associazione Italiana Sindrome X Fragile
- Medical Research Council (MRC) Centre [MR/L010305/1]
- Age UK (Disconnected Mind)
- BBSRC/MRC [MR/K026992/1]
- [G0801418]
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
- Medical Research Council [MR/K026992/1, MR/P005748/1, MR/L010305/1, G0801418, G0802238, MR/M501682/1] Funding Source: researchfish
- BBSRC [BB/F019394/1] Funding Source: UKRI
- MRC [G0801418, MR/P005748/1] Funding Source: UKRI
Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据