Spatial control of avidity regulates initiation and progression of selective autophagy

Abstract: Autophagosomes form at the endoplasmic reticulum in mammals, and between the vacuole and the endoplasmic reticulum in yeast. However, the roles of these sites and the mechanisms regulating autophagosome formation are incompletely understood. Vac8 is required for autophagy and recruits the Atg1 kinase complex to the vacuole. Here we show that Vac8 acts as a central hub to nucleate the phagophore assembly site at the vacuolar membrane during selective autophagy. Vac8 directly recruits the cargo complex via the Atg11 scaffold. In addition, Vac8 recruits the phosphatidylinositol 3-kinase complex independently of autophagy. Cargo-dependent clustering and Vac8-dependent sequestering of these early autophagy factors, along with local Atg1 activation, promote phagophore assembly site assembly at the vacuole. Importantly, ectopic Vac8 redirects autophagosome formation to the nuclear membrane, indicating that the vacuolar membrane is not specifically required. We propose that multiple avidity-driven interactions drive the initiation and progression of selective autophagy

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Nature communications. - 12, 1 (2021) , 7194, ISSN: 2041-1723

Classification
Biowissenschaften, Biologie

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2021
Creator
Hollenstein, David M.
Licheva, Mariya
Konradi, Nicole
Schweida, David
Mancilla, Hector
Mari, Muriel
Reggiori, Fulvio
Kraft, Claudine

DOI
10.1038/s41467-021-27420-3
URN
urn:nbn:de:bsz:25-freidok-2231306
Rights
Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:48 PM CET

Data provider

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Associated

Time of origin

  • 2021

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