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  TECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes

Wetzel, L., Blanchard, S., Rama, S., Beier, V., Kaufmann, A., & Wollert, T. (2020). TECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes. NATURE COMMUNICATIONS, 11: 2993. doi:10.1038/s41467-020-16689-5.

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 Creators:
Wetzel, Lisa1, Author              
Blanchard, Stephane2, Author
Rama, Sowmya2, Author
Beier, Viola1, Author              
Kaufmann, Anna1, Author              
Wollert, Thomas2, Author
Affiliations:
1Wollert, Thomas / Molecular Membrane and Organelle Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565175              
2external, ou_persistent22              

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Free keywords: HOPS COMPLEX; FUSION; DEGRADATION; DEPLETION; PROTEINS; TARGETS
 Abstract: The accumulation of protein aggregates is involved in the onset of many neurodegenerative diseases. Aggrephagy is a selective type of autophagy that counteracts neurodegeneration by degrading such aggregates. In this study, we found that LC3C cooperates with lysosomal TECPR1 to promote the degradation of disease-related protein aggregates in neural stem cells. The N-terminal WD-repeat domain of TECPR1 selectively binds LC3C which decorates matured autophagosomes. The interaction of LC3C and TECPR1 promotes the recruitment of autophagosomes to lysosomes for degradation. Augmented expression of TECPR1 in neural stem cells reduces the number of protein aggregates by promoting their autophagic clearance, whereas knockdown of LC3C inhibits aggrephagy. The PH domain of TECPR1 selectively interacts with PtdIns(4)P to target TECPR1 to PtdIns(4)P containing lysosomes. Exchanging the PH against a tandem-FYVE domain targets TECPR1 ectopically to endosomes. This leads to an accumulation of LC3C autophagosomes at endosomes and prevents their delivery to lysosomes. Many neurodegenerative disorders are characterised by the accumulation of protein aggregates in neurons. Here, the authors show that the lysosomal protein TECPR1 selectively recruits mature autophagosomes via an interaction with LC3C to break down protein aggregates in neural stem cells.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: NATURE COMMUNICATIONS
Source Genre: Journal
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Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 11 Sequence Number: 2993 Start / End Page: - Identifier: ISSN: 2041-1723