The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response against<i>Salmonella</i>

Kageyama, Shun; Omori, Hiroko; Saitoh, Tatsuya; Sone, Takefumi; Guan, Jun‐Lin; Akira, Shizuo; Imamoto, Fumio; Noda, Tetsuji; Yoshimori, Tamotsu

doi:10.1091/mbc.e10-11-0893

Cited by 159 publications

(221 citation statements)

References 52 publications

(87 reference statements)

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“…Such apparently normal recruitment of LC3B to S . Typhimurium in cells failing to restrict bacterial proliferation (Fig 1A and C) may be due to conjugation of LC3 to the remnants of SCV membranes rather than anti‐bacterial phagophores, a phenotype well‐documented for MEFs with defects in upstream autophagy components such as FIP200 or ATG9 (Kageyama et al , 2011). The phenotype in Tbk1 −/− MEFs therefore points to an upstream defect in the autophagy pathway.…”

Section: Resultsmentioning

confidence: 78%

“…Since wortmannin, a potent inhibitor of VPS34, prevents colocalization of WIPI1 but not LC3 with S . Typhimurium (Kageyama et al , 2011), we tested whether TBK1 was similarly required for the recruitment of WIPI proteins to bacteria. We found that GFP‐tagged WIPI1 and WIPI2B but not WIPI3 and WIPI4 accumulated on S .…”

Section: Resultsmentioning

confidence: 99%

“…Apparently normal LC3 recruitment while failing to control the growth of cytosolic S . Typhimurium also occurs in MEFs deficient in FIP200 and ATG9, where it is caused by conjugation of LC3 to the damaged membrane of SCVs rather than to de novo phagophores attacking bacteria (Kageyama et al , 2011). Lack of TBK1, and failure to phosphorylate the LIR motif in optineurin, could result in a similarly subtle but nevertheless functionally important mislocalization of LC3.…”

Section: Discussionmentioning

confidence: 99%

“…WIPI2 is recruited to bacteria via PI(3)P, which initially suggested insufficient PI(3)P in the bacterial vicinity may hinder anti‐bacterial autophagy in Tbk1 −/− MEFs. During autophagy PI(3)P is produced by the VPS34 lipid kinase complex and inhibition of VPS34 with wortmannin or knockout of ATG14L, a subunit of the VPS34 complex, abrogates anti‐bacterial autophagy (Kageyama et al , 2011). However, a defect in PI(3)P production in Tbk1 −/− MEFs can be ruled out since DFCP1, a bona fide probe for the autophagic pool of PI(3)P, is recruited normally to S .…”

Section: Discussionmentioning

confidence: 99%

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Recruitment of TBK 1 to cytosol‐invading Salmonella induces WIPI 2‐dependent antibacterial autophagy

et al. 2016

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Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti‐bacterial autophagy relies on the core autophagy machinery, cargo receptors, and “eat‐me” signals such as galectin‐8 and ubiquitin that label bacteria as autophagy cargo. Anti‐bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti‐bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella‐associated “eat‐me” signals, including host‐derived glycans and K48‐ and K63‐linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host.

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Section: Resultsmentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Recruitment of TBK 1 to cytosol‐invading Salmonella induces WIPI 2‐dependent antibacterial autophagy

et al. 2016

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“…The group led by Sharon Tooze has shown that Atg9 partially colocalizes with recycling endosomes [40] in addition to the previously reported colocalization of Atg9 with the trans-Golgi network and other types of endosomes [26,85]. They also identified TBC1D14 in a screen for putative RabGAP proteins involved in autophagy.…”

Section: The Plasma Membrane and Recycling Endosomesmentioning

confidence: 85%

A current perspective of autophagosome biogenesis

2013

Self Cite

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Autophagy is a bulk degradation system induced by cellular stresses such as nutrient starvation. Its function relies on the formation of double-membrane vesicles called autophagosomes. Unlike other organelles that appear to stably exist in the cell, autophagosomes are formed on demand, and once their formation is initiated, it proceeds surprisingly rapidly. How and where this dynamic autophagosome formation takes place has been a long-standing question, but the discovery of Atg proteins in the 1990's significantly accelerated our understanding of autophagosome biogenesis. In this review, we will briefly introduce each Atg functional unit in relation to autophagosome biogenesis, and then discuss the origin of the autophagosomal membrane with an introduction to selected recent studies addressing this problem.

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Phosphoinositide‐binding proteins in autophagy

Lystad

Simonsen

2016

FEBS Letters

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Edited by Wilhelm JustPhosphoinositides represent a very small fraction of membrane phospholipids, having fast turnover rates and unique subcellular distributions, which make them perfect for initiating local temporal effects. Seven different phosphoinositide species are generated through reversible phosphorylation of the inositol ring of phosphatidylinositol (PtdIns). The negative charge generated by the phosphates provides specificity for interaction with various protein domains that commonly contain a cluster of basic residues. Examples of domains that bind phosphoinositides include PH domains, WD40 repeats, PX domains, and FYVE domains. Such domains often display specificity toward a certain species or subset of phosphoinositides. Here we will review the current literature of different phosphoinositide-binding proteins involved in autophagy.Keywords: autophagy; FYVE; PH; phosphoinositide; PX AutophagyAutophagy is the process by which cellular components are transported to the lysosome (or the yeast vacuole) for degradation to provide cellular homeostasis and quality control. There are three main forms of autophagy, namely microautophagy, which involves a direct engulfment of cytosolic cargo by the endosomal or lysosomal/vacuolar membrane, chaperone-mediated autophagy (CMA), involving lysosomal translocation of cytosolic protein cargo, and macroautophagy, a vesicle transport pathway where cargo is sequestered into double-membrane autophagosomes which undergo fusion with endosomes and/or the lysosome/vacuole. Autophagy is induced upon cellular stress (e.g., starvation) to facilitate cell survival by providing building blocks that can be used to produce essential molecules and generate energy. However, autophagy also serves an important quality control function under basal conditions by selective clearance of damaged or dysfunctional cellular components [1].Macroautophagy (hereafter autophagy) involves nucleation of a phagophore membrane (also called the isolation membrane) from specific phosphatidyl inositol 3-phosphate (PtdIns3P)-enriched structures, called the phagophore assembly site (PAS, a peri-vacuolar structure) in yeast and the omegasome (associated with the endoplasmic reticulum, ER) in mammals. Typically, there is only a single PAS in yeast, while several ER-associated omegasomes are detected upon Abbreviations ALFY, autophagy-linked FYVE protein; Arf6, adenosine diphosphate ribosylation factor 6; ATG, autophagy-related; BATS, biotin and thiamin synthesis-associated domain; Cvt, cytoplasm-to-vacuole; DFCP1, double FYVE-containing protein 1; ER, endoplasmic reticulum; FYCO1, FYVE and coiled-coil domain-containing 1; GRAM, glycosyltransferases Rab-like GTPase activators and myotubularins; HOPS, homotypic fusion and protein sorting; Hsv2, homologous with swollen vacuole phenotype 2; LIR, LC3-interacting region; MTMR3, myotubularin-related protein 3; mTORC1, mechanistic target of rapamycin complex 1; PA, phosphatidic acid; PAS, phagophore assembly site; PDPK1, 3-phosphoinositide-dependent protein kinase ...

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The LC3 recruitment mechanism is separate from Atg9L1-dependent membrane formation in the autophagic response againstSalmonella

Cited by 159 publications

References 52 publications

Recruitment of TBK 1 to cytosol‐invading Salmonella induces WIPI 2‐dependent antibacterial autophagy

Recruitment of TBK 1 to cytosol‐invading Salmonella induces WIPI 2‐dependent antibacterial autophagy

A current perspective of autophagosome biogenesis

Phosphoinositide‐binding proteins in autophagy

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