Cullin-3 regulates late endosome maturation

被引：58

作者：

Huotari, Jatta ^{[1
]}

Meyer-Schaller, Nathalie ^{[1
]}

Hubner, Michaela ^{[1
]}

Stauffer, Sarah ^{[1
]}

Katheder, Nadja ^{[1
]}

Horvath, Peter ^{[2
]}

Mancini, Roberta ^{[1
]}

Helenius, Ari ^{[1
]}

Peter, Matthias ^{[1
]}

机构：

[1] ETH, Inst Biochem, CH-8093 Zurich, Switzerland

[2] ETH, Dept Biol, Light Microscopy Ctr, CH-8093 Zurich, Switzerland

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 03期

基金：

欧洲研究理事会; 瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

membrane trafficking; multivesicular body; virus entry; endocytosis; influenza virus; SEMLIKI FOREST VIRUS; INFLUENZA-VIRUS; MULTIVESICULAR BODIES; MEMBRANE-FUSION; ENTRY; TRANSPORT; UBIQUITIN; RECEPTOR; ENDOCYTOSIS; HEMAGGLUTININ;

D O I：

10.1073/pnas.1118744109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Cullin-3 (Cul3) functions as a scaffolding protein in the Bric-a-brac, Tramtrack, Broad-complex (BTB)-Cul3-Rbx1 ubiquitin E3 ligase complex. Here, we report a previously undescribed role for Cul3 complexes in late endosome (LE) maturation. RNAi-mediated depletion of Cul3 results in a trafficking defect of two cargoes of the endolysosomal pathway, influenza A virus (IAV) and epidermal growth factor receptor (EGFR). IAV is able to reach an acidic endosomal compartment, coinciding with LE/lysosome (LY) markers. However, it remains trapped or the capsid is unable to uncoat after penetration into the cytosol. Similarly, activation and subsequent ubiquitination of EGFR appear normal, whereas downstream EGFR degradation is delayed and its ligand EGF accumulates in LE/LYs. Indeed, Cul3-depleted cells display severe morphological defects in LEs that could account for these trafficking defects; they accumulate acidic LE/LYs, and some cells become highly vacuolated, with enlarged Rab7-positive endosomes. Together, these results suggest a crucial role of Cul3 in regulating late steps in the endolysosomal trafficking pathway.

引用

页码：823 / 828

页数：6

共 43 条

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