Open AccessAtg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome
Author(s) -
Sunandini Chandra,
Philip J. Mannino,
David J Thaller,
Nicholas R. Ader,
Megan C. King,
Thomas J. Melia,
C. Patrick Lusk
Publication year - 2021
Publication title -
the journal of cell biology/the journal of cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.414
H-Index - 380
eISSN - 1540-8140
pISSN - 0021-9525
DOI - 10.1083/jcb.202103030
Subject(s) - inner membrane , autophagosome , vesicle , microbiology and biotechnology , nuclear localization sequence , cytosol , nuclear pore , biology , transmembrane protein , biophysics , autophagy , nucleus , chemistry , membrane , biochemistry , receptor , mitochondrion , apoptosis , enzyme
Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope–localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside–in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.