Antibacterial autophagy occurs at PtdIns(3)P-enriched domains of the endoplasmic reticulum and requires Rab1 GTPase

被引：96

作者：

Huang, Ju ^{[1
]}

Birmingham, Cheryl L. ^{[1
,2
]}

Shahnazari, Shahab ^{[1
,2
]}

Shiu, Jessica ^{[1
]}

Zheng, Yiyu T. ^{[1
,2
]}

Smith, Adam C. ^{[1
,2
]}

Campellone, Kenneth G. ^{[4
]}

Heo, Won Do ^{[5
,6
]}

Gruenheid, Samantha ^{[7
]}

Meyer, Tobias ^{[8
]}

Welch, Matthew D. ^{[4
]}

Ktistakis, Nicholas T. ^{[9
]}

Kim, Peter K. ^{[1
]}

Klionsky, Daniel J. ^{[10
,11
,12
]}

Brumell, John H. ^{[1
,2
,3
]}

机构：

[1] Univ Toronto, Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada

[2] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada

[3] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada

[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[5] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

[6] Korea Adv Inst Sci & Technol, KI BioCentury, Taejon 305701, South Korea

[7] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada

[8] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[9] Babraham Inst, Signalling Programme, Cambridge, England

[10] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[11] Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA

[12] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

来源：

AUTOPHAGY | 2011年 / 7卷 / 01期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

autophagy; DFCP1; Rab1; Salmonella; ER-to-golgi trafficking; SALMONELLA-CONTAINING VACUOLE; GENOME-WIDE ASSOCIATION; PHOSPHATIDYLINOSITOL; 3-PHOSPHATE; GOLGI COMPARTMENTS; ADAPTIVE IMMUNITY; EPITHELIAL-CELLS; CROHN-DISEASE; CIS-GOLGI; TYPHIMURIUM; TRANSPORT;

D O I：

10.4161/auto.7.1.13840

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Autophagy mediates the degradation of cytoplasmic components in eukaryotic cells and plays a key role in immunity. The mechanism of autophagosome formation is not clear. Here we examined two potential membrane sources for antibacterial autophagy: the ER and mitochondria. DFCP1, a marker of specialized ER domains known as 'omegasomes,' associated with Salmonella-containing autophagosomes via its PtdIns(3)P and ER-binding domains, while a mitochondrial marker (cytochrome b5-GFP) did not. Rab1 also localized to autophagosomes, and its activity was required for autophagosome formation, clearance of protein aggregates and peroxisomes, and autophagy of Salmonella. Overexpression of Rab1 enhanced antibacterial autophagy. The role of Rab1 in antibacterial autophagy was independent of its role in ER-to-Golgi transport. Our data suggest that antibacterial autophagy occurs at omegasomes and reveal that the Rab1 GTPase plays a crucial role in mammalian autophagy.

引用

页码：17 / 26

页数：10

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