Atg11 tethers Atg9 vesicles to initiate selective autophagy.

Autophagy recycles cytoplasmic components by sequestering them in double membrane-surrounded autophagosomes. The two proteins Atg11 and Atg17 are scaffolding components of the Atg1 kinase complex. Atg17 recruits and tethers Atg9-donor vesicles, and the corresponding Atg1 kinase complex induces the f...

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Main Authors: Nena Matscheko, Peter Mayrhofer, Yijian Rao, Viola Beier, Thomas Wollert
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-07-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3000377
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author Nena Matscheko
Peter Mayrhofer
Yijian Rao
Viola Beier
Thomas Wollert
author_facet Nena Matscheko
Peter Mayrhofer
Yijian Rao
Viola Beier
Thomas Wollert
author_sort Nena Matscheko
collection DOAJ
description Autophagy recycles cytoplasmic components by sequestering them in double membrane-surrounded autophagosomes. The two proteins Atg11 and Atg17 are scaffolding components of the Atg1 kinase complex. Atg17 recruits and tethers Atg9-donor vesicles, and the corresponding Atg1 kinase complex induces the formation of nonselective autophagosomes. Atg11 initiates selective autophagy and coordinates the switch to nonselective autophagy by recruiting Atg17. The molecular function of Atg11 remained, however, less well understood. Here, we demonstrate that Atg11 is activated by cargo through a direct interaction with autophagy receptors. Activated Atg11 dimerizes and tethers Atg9 vesicles, which leads to the nucleation of phagophores in direct vicinity of cargo. Starvation reciprocally regulates the activity of both tethering factors by initiating the degradation of Atg11 while Atg17 is activated. This allows Atg17 to sequester and tether Atg9 vesicles independent of cargo to nucleate nonselective phagophores. Our data reveal insights into the molecular mechanisms governing cargo selection and specificity in autophagy.
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spelling doaj.art-6e80543085e64893bc99d1dac9ec4fed2022-12-21T18:40:18ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-07-01177e300037710.1371/journal.pbio.3000377Atg11 tethers Atg9 vesicles to initiate selective autophagy.Nena MatschekoPeter MayrhoferYijian RaoViola BeierThomas WollertAutophagy recycles cytoplasmic components by sequestering them in double membrane-surrounded autophagosomes. The two proteins Atg11 and Atg17 are scaffolding components of the Atg1 kinase complex. Atg17 recruits and tethers Atg9-donor vesicles, and the corresponding Atg1 kinase complex induces the formation of nonselective autophagosomes. Atg11 initiates selective autophagy and coordinates the switch to nonselective autophagy by recruiting Atg17. The molecular function of Atg11 remained, however, less well understood. Here, we demonstrate that Atg11 is activated by cargo through a direct interaction with autophagy receptors. Activated Atg11 dimerizes and tethers Atg9 vesicles, which leads to the nucleation of phagophores in direct vicinity of cargo. Starvation reciprocally regulates the activity of both tethering factors by initiating the degradation of Atg11 while Atg17 is activated. This allows Atg17 to sequester and tether Atg9 vesicles independent of cargo to nucleate nonselective phagophores. Our data reveal insights into the molecular mechanisms governing cargo selection and specificity in autophagy.https://doi.org/10.1371/journal.pbio.3000377
spellingShingle Nena Matscheko
Peter Mayrhofer
Yijian Rao
Viola Beier
Thomas Wollert
Atg11 tethers Atg9 vesicles to initiate selective autophagy.
PLoS Biology
title Atg11 tethers Atg9 vesicles to initiate selective autophagy.
title_full Atg11 tethers Atg9 vesicles to initiate selective autophagy.
title_fullStr Atg11 tethers Atg9 vesicles to initiate selective autophagy.
title_full_unstemmed Atg11 tethers Atg9 vesicles to initiate selective autophagy.
title_short Atg11 tethers Atg9 vesicles to initiate selective autophagy.
title_sort atg11 tethers atg9 vesicles to initiate selective autophagy
url https://doi.org/10.1371/journal.pbio.3000377
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AT yijianrao atg11tethersatg9vesiclestoinitiateselectiveautophagy
AT violabeier atg11tethersatg9vesiclestoinitiateselectiveautophagy
AT thomaswollert atg11tethersatg9vesiclestoinitiateselectiveautophagy