Co-immunoprecipitation with Tau isoform-specific antibodies reveals distinct protein interactions and highlights a putative role for 2N Tau in disease

Liu, Chang, Song, Xiaomin, Nisbet, Rebecca and Goetz, Juergen (2016) Co-immunoprecipitation with Tau isoform-specific antibodies reveals distinct protein interactions and highlights a putative role for 2N Tau in disease. Journal of Biological Chemistry, 291 15: 8173-8188. doi:10.1074/jbc.M115.641902


Author Liu, Chang
Song, Xiaomin
Nisbet, Rebecca
Goetz, Juergen
Title Co-immunoprecipitation with Tau isoform-specific antibodies reveals distinct protein interactions and highlights a putative role for 2N Tau in disease
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2016-04-08
Year available 2016
Sub-type Article (original research)
DOI 10.1074/jbc.M115.641902
Open Access Status DOI
Volume 291
Issue 15
Start page 8173
End page 8188
Total pages 16
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biology Inc.
Language eng
Subject 1303 Biochemistry
1312 Molecular Biology
1307 Cell Biology
Abstract Alternative splicing generates multiple isoforms of the microtubule-associated protein Tau, but little is known about their specific function. In the adult mouse brain, three Tau isoforms are expressed that contain either 0, 1, or 2 N-terminal inserts (0N, 1N, and 2N). We generated Tau isoform-specific antibodies and performed co-immunoprecipitations followed by tandem mass tag multiplexed quantitative mass spectrometry. We identified novel Tau-interacting proteins of which one-half comprised membrane-bound proteins, localized to the plasma membrane, mitochondria, and other organelles. Tau was also found to interact with proteins involved in presynaptic signal transduction. MetaCore analysis revealed one major Tau interaction cluster that contained 33 Tau pulldown proteins. To explore the pathways in which these proteins are involved, we conducted an ingenuity pathway analysis that revealed two significant overlapping pathways, “cell-to-cell signaling and interaction” and “neurological disease.” The functional enrichment tool DAVID showed that in particular the 2N Tau-interacting proteins were specifically associated with neurological disease. Finally, for a subset of Tau interactions (apolipoprotein A1 (apoA1), apoE, mitochondrial creatine kinase U-type, β-synuclein, synaptogyrin-3, synaptophysin, syntaxin 1B, synaptotagmin, and synapsin 1), we performed reverse co-immunoprecipitations, confirming the preferential interaction of specific isoforms. For example, apoA1 displayed a 5-fold preference for the interaction with 2N, whereas β-synuclein showed preference for 0N. Remarkably, a reverse immunoprecipitation with apoA1 detected only the 2N isoform. This highlights distinct protein interactions of the different Tau isoforms, suggesting that they execute different functions in brain tissue.
Keyword Alzheimer disease
Apolipoprotein
Protein/protein interaction
Tau protein (Tau)
Tauopathy
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID ACT900116
DP13300101932
APP1037746
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 18 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 08 May 2016, 10:27:43 EST by System User on behalf of Clem Jones Centre for Ageing Dementia Research