FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates

Abstract The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, and ablation of either function has been linked to neuroinflammatory or degenerative diseases. Autophagy is an intracellular process that recycles old or damaged proteins and organelles. In recent years...

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Autores principales:	David Schlütermann, Niklas Berleth, Jana Deitersen, Nora Wallot-Hieke, Olena Friesen, Wenxian Wu, Fabian Stuhldreier, Yadong Sun, Lena Berning, Annabelle Friedrich, María José Mendiburo, Christoph Peter, Constanze Wiek, Helmut Hanenberg, Anja Stefanski, Kai Stühler, Björn Stork
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6972ad6fb1594ad394a0391385e1a71d
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spelling	oai:doaj.org-article:6972ad6fb1594ad394a0391385e1a71d2021-12-02T18:34:13ZFIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates10.1038/s41598-021-92408-42045-2322https://doaj.org/article/6972ad6fb1594ad394a0391385e1a71d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92408-4https://doaj.org/toc/2045-2322Abstract The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, and ablation of either function has been linked to neuroinflammatory or degenerative diseases. Autophagy is an intracellular process that recycles old or damaged proteins and organelles. In recent years, the TBK1-dependent regulation of autophagy pathways has been characterized. However, the autophagy-dependent regulation of TBK1 activity awaits further clarification. Here, we observed that TBK1 is recruited to SQSTM1/p62-containing aggregates via the selective autophagy receptor TAX1BP1. In these aggregates, TBK1 phosphorylates SQSTM1/p62 at serine 403 and thus presumably regulates the efficient engulfment and clearance of these structures. We found that TBK1 activation is strongly increased if FIP200, a component of the autophagy-inducing ULK1 complex, is not present or cannot bind to TAX1BP1. Given our collective findings, we hypothesize that FIP200 ensures the inducible activation of TBK1 at SQSTM1/p62 condensates.David SchlütermannNiklas BerlethJana DeitersenNora Wallot-HiekeOlena FriesenWenxian WuFabian StuhldreierYadong SunLena BerningAnnabelle FriedrichMaría José MendiburoChristoph PeterConstanze WiekHelmut HanenbergAnja StefanskiKai StühlerBjörn StorkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Schlütermann Niklas Berleth Jana Deitersen Nora Wallot-Hieke Olena Friesen Wenxian Wu Fabian Stuhldreier Yadong Sun Lena Berning Annabelle Friedrich María José Mendiburo Christoph Peter Constanze Wiek Helmut Hanenberg Anja Stefanski Kai Stühler Björn Stork FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
description	Abstract The protein kinase TBK1 is a central regulator of innate immune responses and autophagy, and ablation of either function has been linked to neuroinflammatory or degenerative diseases. Autophagy is an intracellular process that recycles old or damaged proteins and organelles. In recent years, the TBK1-dependent regulation of autophagy pathways has been characterized. However, the autophagy-dependent regulation of TBK1 activity awaits further clarification. Here, we observed that TBK1 is recruited to SQSTM1/p62-containing aggregates via the selective autophagy receptor TAX1BP1. In these aggregates, TBK1 phosphorylates SQSTM1/p62 at serine 403 and thus presumably regulates the efficient engulfment and clearance of these structures. We found that TBK1 activation is strongly increased if FIP200, a component of the autophagy-inducing ULK1 complex, is not present or cannot bind to TAX1BP1. Given our collective findings, we hypothesize that FIP200 ensures the inducible activation of TBK1 at SQSTM1/p62 condensates.
format	article
author	David Schlütermann Niklas Berleth Jana Deitersen Nora Wallot-Hieke Olena Friesen Wenxian Wu Fabian Stuhldreier Yadong Sun Lena Berning Annabelle Friedrich María José Mendiburo Christoph Peter Constanze Wiek Helmut Hanenberg Anja Stefanski Kai Stühler Björn Stork
author_facet	David Schlütermann Niklas Berleth Jana Deitersen Nora Wallot-Hieke Olena Friesen Wenxian Wu Fabian Stuhldreier Yadong Sun Lena Berning Annabelle Friedrich María José Mendiburo Christoph Peter Constanze Wiek Helmut Hanenberg Anja Stefanski Kai Stühler Björn Stork
author_sort	David Schlütermann
title	FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
title_short	FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
title_full	FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
title_fullStr	FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
title_full_unstemmed	FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates
title_sort	fip200 controls the tbk1 activation threshold at sqstm1/p62-positive condensates
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6972ad6fb1594ad394a0391385e1a71d
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_version_	1718377866007150592

FIP200 controls the TBK1 activation threshold at SQSTM1/p62-positive condensates

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