Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau
| Autor: | Lena Wischhof, Aasha Adhikari, Mrityunjoy Mondal, Anaïs Marsal-Cots, Jacek Biernat, Eva Maria Mandelkow, Eckhard Mandelkow, Dan Ehninger, Pierluigi Nicotera, Daniele Bano |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Proteomics
autophagy Gene Expression tau Proteins Endoplasmic Reticulum Biochemistry SAH hydrolase–like protein 1 (AHCYL1/IRBIT) metabolism [Endoplasmic Reticulum] Humans Lectins C-Type ddc:610 Molecular Biology genetics [Lectins C-Type] Membrane Proteins Cell Biology metabolism [tau Proteins] human protein microarray metabolism [Lectins C-Type] genetics [Membrane Proteins] genetics [tau Proteins] microtubule-associated protein tau genetics [Endoplasmic Reticulum] Alzheimer’s disease metabolism [Membrane Proteins] Protein Binding |
| Zdroj: | The journal of biological chemistry 298(4), 101774 (2022). doi:10.1016/j.jbc.2022.101774 The Journal of Biological Chemistry |
| DOI: | 10.1016/j.jbc.2022.101774 |
| Popis: | Microtubule-associated protein tau is a naturally unfolded protein that can modulate a vast array of physiological processes through direct or indirect binding with molecular partners. Aberrant tau homeostasis has been implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease (AD). In this study, we performed an unbiased high-content protein profiling assay by incubating recombinant human tau on microarrays containing thousands of human polypeptides. Among the putative tau-binding partners, we identify S-adenosylhomocysteine hydrolase-like protein 1/ inositol 1,4,5-trisphosphate receptor (IP3R) binding protein (AHCYL1/IRBIT), a member of the S-adenosylhomocysteine hydrolase family and a previously described modulator of IP3R activity. Using co-immunoprecipitation assays, we show that endogenous as well as overexpressed tau can physically interact with AHCYL1/IRBIT in brain tissues and cultured cells. Proximity ligation assay (PLA) experiments demonstrate that tau overexpression may modify the close localization of AHCYL1/IRBIT to IP3R at the endoplasmic reticulum (ER). Together, our experimental evidence indicates that tau interacts with AHCYL1/IRBIT and potentially modulates AHCYL1/IRBIT function. |
| Databáze: | OpenAIRE |
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