Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome

被引：20

作者：

Chandra, Sunandini ^{[1
]}

Mannino, Philip J. ^{[1
]}

Thaller, David J. ^{[1
]}

Ader, Nicholas R. ^{[1
]}

King, Megan C. ^{[1
]}

Melia, Thomas J. ^{[1
]}

Lusk, C. Patrick ^{[1
]}

机构：

[1] Yale Sch Med, Dept Cell Biol, New Haven, CT USA

来源：

JOURNAL OF CELL BIOLOGY | 2021年 / 220卷 / 12期

基金：

美国国家卫生研究院;

关键词：

SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; CARGO RECOGNITION; PORE COMPLEXES; ENVELOPE; PROTEINS; YEAST; GENE; OVEREXPRESSION;

D O I：

10.1083/jcb.202103030

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：27

共 97 条

[21] Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S-cerevisiae, causes proliferation of the endoplasmic reticulum membrane [J].