TY  - JOUR
AU  - Wischhof, Lena
AU  - Adhikari, Aasha
AU  - Mondal, Mrityunjoy
AU  - Marsal Cots, Anais
AU  - Biernat, Jacek
AU  - Mandelkow, Eva Maria
AU  - Mandelkow, Eckhard
AU  - Ehninger, Dan
AU  - Nicotera, Pierluigi
AU  - Bano, Daniele
TI  - Unbiased proteomic profiling reveals the IP3R modulator AHCYL1/IRBIT as a novel interactor of microtubule-associated protein tau.
JO  - The journal of biological chemistry
VL  - 298
IS  - 4
SN  - 0021-9258
CY  - Bethesda, MD.
PB  - American Soc. for Biochemistry and Molecular Biology
M1  - DZNE-2022-00468
SP  - 101774
PY  - 2022
N1  - (CC BY)
AB  - 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.
KW  - Endoplasmic Reticulum: genetics
KW  - Endoplasmic Reticulum: metabolism
KW  - Gene Expression
KW  - Humans
KW  - Lectins, C-Type: genetics
KW  - Lectins, C-Type: metabolism
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: metabolism
KW  - Protein Binding
KW  - Proteomics
KW  - tau Proteins: genetics
KW  - tau Proteins: metabolism
KW  - Alzheimer’s disease (Other)
KW  - SAH hydrolase–like protein 1 (AHCYL1/IRBIT) (Other)
KW  - autophagy (Other)
KW  - human protein microarray (Other)
KW  - microtubule-associated protein tau (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:35218773
C2  - pmc:PMC8956953
DO  - DOI:10.1016/j.jbc.2022.101774
UR  - https://pub.dzne.de/record/163729
ER  -