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ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling

Object's details: ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling

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Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling
Creator:
Asaro, Antonino;
Sinha, Indranil;
Bakun, Magda;
Kalnytska, Oleksandra;
Carlo-Spiewok, Anne-Sophie;
Rubel, Tymon;
Rozeboom, Annemieke;
Dadlez, Michal;
Kaminska, Bozena;
Aronica, Eleonora;
Malik, Anna R.;
Willnow, Thomas E.
Description:
Sortilin is a neuronal receptor for apolipoprotein E (apoE). Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with the apoE3 variant but is lost with the apoE4 variant, the main risk factor for Alzheimer's disease (AD). Here, we elucidated steps in cellular handling of lipids through sortilin, and why they are disrupted by apoE4. Combining unbiased proteome screens with analyses in mouse models, we uncover interaction of sortilin with fatty acid-binding protein 7 (FABP7), the intracellular carrier for PUFA in the brain. In the presence of apoE3, sortilin promotes functional expression of FABP7 and its ability to elicit lipid-dependent gene transcription. By contrast, apoE4 binding blocks sortilin-mediated sorting, causing catabolism of FABP7 and impairing lipid signaling. Reduced FABP7 levels in the brain of AD patients expressing apoE4 substantiate the relevance of these interactions for neuronal lipid homeostasis. Taken together, we document interaction of sortilin with mediators of extracellular and intracellular lipid transport that provides a mechanistic explanation for loss of a neuroprotective lipid metabolism in AD.
Object availability:
free access
Date:
2021
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Relation: http://eprints.ibb.waw.pl/2102 ;https://journals.biologists.com/jcs/article/134/20/jcs258894/272562/ApoE4-disrupts-interaction-of-sortilin-with-fatty ;DOI: 10.1242/jcs.258894
Subject:
QH301 Biology
Identifier: http://eprints.ibb.waw.pl/2102/2/jcs258894.pdf ;
Asaro, Antonino and Sinha, Indranil and Bakun, Magda and Kalnytska, Oleksandra and Carlo-Spiewok, Anne-Sophie and Rubel, Tymon and Rozeboom, Annemieke and Dadlez, Michal and Kaminska, Bozena and Aronica, Eleonora and Malik, Anna R. and Willnow, Thomas E. (2021) ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling. Journal of Cell Science, 134 (20). jcs258894. ISSN 0021-9533
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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