Journal Article DZNE-2022-00468

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Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau.

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2022
American Soc. for Biochemistry and Molecular Biology Bethesda, MD.

The journal of biological chemistry 298(4), 101774 () [10.1016/j.jbc.2022.101774]

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Abstract: 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. 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 SAH hydrolase-like protein 1/inositol 1,4,5-trisphosphate receptor (IP3R)-binding protein (AHCYL1/IRBIT), a member of the SAH hydrolase family and a previously described modulator of IP3R activity. Using coimmunoprecipitation 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 experiments demonstrate that tau overexpression may modify the close localization of AHCYL1/IRBIT to IP3R at the endoplasmic reticulum. Together, our experimental evidence indicates that tau interacts with AHCYL1/IRBIT and potentially modulates AHCYL1/IRBIT function.

Keyword(s): Endoplasmic Reticulum: genetics (MeSH) ; Endoplasmic Reticulum: metabolism (MeSH) ; Gene Expression (MeSH) ; Humans (MeSH) ; Lectins, C-Type: genetics (MeSH) ; Lectins, C-Type: metabolism (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Protein Binding (MeSH) ; Proteomics (MeSH) ; tau Proteins: genetics (MeSH) ; tau Proteins: metabolism (MeSH) ; Alzheimer’s disease ; SAH hydrolase–like protein 1 (AHCYL1/IRBIT) ; autophagy ; human protein microarray ; microtubule-associated protein tau

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Contributing Institute(s):
  1. Aging and neurodegeneration (AG Bano)
  2. Structural Principles of Neurodegeneration (AG Mandelkow 1)
  3. Cell and Animal Models of Neurodegeneration (AG Mandelkow 2)
  4. Translational Biogerontology (AG Ehninger)
  5. Scientific board (Scientific board)
Research Program(s):
  1. 351 - Brain Function (POF4-351) (POF4-351)
  2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022
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Medline ; Creative Commons Attribution CC BY 4.0 ; OpenAccess ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Institute Collections > BN DZNE > BN DZNE-Scientific board
Document types > Articles > Journal Article
Institute Collections > BN DZNE > BN DZNE-AG Mandelkow 2
Institute Collections > BN DZNE > BN DZNE-AG Mandelkow 1
Institute Collections > BN DZNE > BN DZNE-AG Ehninger
Institute Collections > BN DZNE > BN DZNE-AG Bano
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 Record created 2022-04-21, last modified 2024-03-20


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