Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome.
Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome.
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DOI：
10.1083/jcb.202103030
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发表时间：
2021-12-06
期刊：
影响因子：
--
通讯作者：
Lusk CP
中科院分区：
文献类型：
--
作者：
Chandra S;Mannino PJ;Thaller DJ;Ader NR;King MC;Melia TJ;Lusk CP
Chandra，Mannino，Thaller等人。为一种由外而内的核自噬模型提供证据，该模型使用常驻的外核膜货物适配器来靶向跨越核包膜管腔的内核膜。内核膜被选择性地结合到腔内小泡中，以输送到自噬小体。翻转核和核内膜(INM)成分的机制仍未完全确定。我们探索了INM的成分是如何由细胞质自噬装置通过跨膜核膜定位的货物适配器ATG39来选择的。Split-GFP报道显示，Atg39定位于外核膜(ONM)，从而靶向穿过核包膜管腔的INM。与此一致，同时提供核膜定位和膜重塑活性的序列元件被映射到Atg39腔结构域；这些腔基序是自噬介导的完整INM蛋白降解所必需的。有趣的是，相关的光学和电子显微镜显示，Atg39的过度表达导致ONM的扩张和核包膜内腔内INM来源的囊泡网络的包围。因此，我们提出了一个由外而内的吞核模型，在该模型中，INM被运送到核包膜管腔中的小泡中，这可以被自噬小体靶向。
Chandra, Mannino, Thaller et al. provide evidence for an outside–in model of nuclear autophagy that employs a resident outer nuclear membrane cargo adaptor to target the inner nuclear membrane across the nuclear envelope lumen. The inner nuclear membrane is selectively incorporated into intralumenal vesicles for delivery to the autophagosome. 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.
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影响因子：
3.3
作者：
Borah S;Thaller DJ;Hakhverdyan Z;Rodriguez EC;Isenhour AW;Rout MP;King MC;Lusk CP
通讯作者：
Lusk CP
影响因子：
25
作者：
Chou CC;Zhang Y;Umoh ME;Vaughan SW;Lorenzini I;Liu F;Sayegh M;Donlin-Asp PG;Chen YH;Duong DM;Seyfried NT;Powers MA;Kukar T;Hales CM;Gearing M;Cairns NJ;Boylan KB;Dickson DW;Rademakers R;Zhang YJ;Petrucelli L;Sattler R;Zarnescu DC;Glass JD;Rossoll W
通讯作者：
Rossoll W
影响因子：
11.1
作者：
Harhouri K;Navarro C;Depetris D;Mattei MG;Nissan X;Cau P;De Sandre-Giovannoli A;Lévy N
通讯作者：
Lévy N
影响因子：
17.1
作者：
通讯作者：
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DOI：
10.1073/pnas.2008923117
发表时间：
2020-08-04
影响因子：
11.1
作者：
Chen, Shuliang;Mari, Muriel;Ferro-Novick, Susan
通讯作者：
Ferro-Novick, Susan