Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin

被引：231

作者：

Fujita, Naonobu ^{[1
,2
]}

Morita, Eiji ^{[3
]}

Itoh, Takashi ^{[8
]}

Tanaka, Atsushi ^{[2
]}

Nakaoka, Megumi ^{[2
]}

Osada, Yuki ^{[1
]}

Umemoto, Tetsuo ^{[2
]}

Saitoh, Tatsuya ^{[4
,5
]}

Nakatogawa, Hitoshi ^{[7
]}

Kobayashi, Shouhei ^{[9
]}

Haraguchi, Tokuko ^{[9
]}

Guan, Jun-Lin ^{[10
]}

Iwai, Kazuhiro ^{[11
]}

Tokunaga, Fuminori ^{[12
]}

Saito, Kazunobu ^{[6
]}

Ishibashi, Koutaro ^{[8
]}

Akira, Shizuo ^{[4
,5
]}

Fukuda, Mitsunori ^{[8
]}

Noda, Takeshi ^{[1
,2
]}

Yoshimori, Tamotsu ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Genet, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Frontier Biosci, Lab Intracellular Membrane Dynam, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Microbial Dis Res Inst, Dept Mol Virol, Suita, Osaka 5650871, Japan

[4] Osaka Univ, WPI Immunol Frontier Res Ctr, Dept Host Def, Suita, Osaka 5650871, Japan

[5] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan

[6] Osaka Univ, Microbial Dis Res Inst, Core Instrumentat Facil, Suita, Osaka 5650871, Japan

[7] Tokyo Inst Technol, Frontier Res Ctr, Yokohama, Kanagawa 2268503, Japan

[8] Tohoku Univ, Grad Sch Life Sci, Dept Dev Biol & Neurosci, Sendai, Miyagi 9808578, Japan

[9] Natl Inst Informat & Commun Technol, Adv ICT Res Inst Kobe, Kobe, Hyogo 6512492, Japan

[10] Univ Michigan, Sch Med, Dept Internal Med MMG, Ann Arbor, MI 48109 USA

[11] Kyoto Univ, Grad Sch Med, Dept Mol & Cellular Physiol, Sakyo Ku, Kyoto 6068501, Japan

[12] Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gunma 3718512, Japan

来源：

JOURNAL OF CELL BIOLOGY | 2013年 / 203卷 / 01期

关键词：

CONJUGATING ENZYME; COMPLEX; PROTEIN; MEMBRANE; CELLS; BIOGENESIS; LIPIDATION; RESTRICTS; TARGETS; ATG16L1;

D O I：

10.1083/jcb.201304188

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Although ubiquitin is thought to be important for the autophagic sequestration of invading bacteria (also called xenophagy), its precise role remains largely enigmatic. Here we determined how ubiquitin is involved in this process. After invasion, ubiquitin is conjugated to host cellular proteins in endosomes that contain Salmonella or transfection reagent-coated latex (polystyrene) beads, which mimic invading bacteria. Ubiquitin is recognized by the autophagic machinery independently of the LC3-ubiquitin interaction through adaptor proteins, including a direct interaction between ubiquitin and Atg16L1. To ensure that invading pathogens are captured and degraded, Atg16L1 targeting is secured by two backup systems that anchor Atg16L1 to ubiquitin-decorated endosomes. Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3.

引用

页码：115 / 128

页数：14

共 45 条

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