Noncanonical autophagy: one small step for LC3, one giant leap for immunity

Mehta, Preeti; Hénault, Jill; Kolbeck, Roland; Sanjuán, Miguel A. F.

doi:10.1016/j.coi.2013.10.012

Cited by 101 publications

(87 citation statements)

References 49 publications

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“…7F,G), suggesting that autophagy may also be involved in the clearance of dying cells (Mehta et al, 2014). Taken together, these results imply that SG elimination might contribute to GSC maintenance partly through local recycling of nutrients.…”

Section: Sg Death Is Associated With Phagocytosis and Jnk-pathway Actmentioning

confidence: 50%

The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

Yang

Yamashita

2015

Development

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How tissues adapt to varying nutrient conditions is of fundamental importance for robust tissue homeostasis throughout the life of an organism, but the underlying mechanisms are poorly understood. Here, we show that Drosophila testis responds to protein starvation by eliminating transit-amplifying spermatogonia (SG) while maintaining a reduced pool of actively proliferating germline stem cells (GSCs). During protein starvation, SG die in a manner that is mediated by the apoptosis of somatic cyst cells (CCs) that encapsulate SG and regulate their development. Strikingly, GSCs cannot be maintained during protein starvation when CC-mediated SG death is inhibited, leading to an irreversible collapse of tissue homeostasis. We propose that the regulated elimination of transit-amplifying cells is essential to preserve stem cell function and tissue homeostasis during protein starvation.

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Section: Sg Death Is Associated With Phagocytosis and Jnk-pathway Actmentioning

confidence: 50%

The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

Yang

Yamashita

2015

Development

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“…8C). It has been demonstrated that LC3 can also be recruited to single membrane phagosomes or vesicles to assist in lysosomal fusion in a process denoted as LC3-associated phagocytosis (LAP) (73)(74)(75)(76). Pathogens such as Burkholderia pseudomallei and Mycobacterium marinum have elicited LAP features in RAW264.7-GFP-LC3 macrophages (77)(78)(79).…”

Section: Discussionmentioning

confidence: 99%

The Role of Autophagy during Group B Streptococcus Infection of Blood-Brain Barrier Endothelium

Cutting¹,

Rosario²,

Mu³

et al. 2014

Journal of Biological Chemistry

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Background: Penetration of brain endothelium by Group B streptococcus (GBS) is the first step in the development of meningitis. Results: Autophagy is activated in response to GBS infection. Conclusion: Autophagy induction occurs through GBS toxin expression, while key autophagic proteins contribute to GBS destruction. Significance: Understanding the role of autophagy in brain endothelium may inform novel strategies to prevent the pathogenesis of bacterial meningitis.

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“…3,4 Through this pathway, MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) is lipidated onto a variety of single-membrane vacuoles, including phagosomes, macropinosomes, and entotic vacuoles and is important for innate immunity and vision. 3,5,6 Single-membrane LC3 lipidation requires components of the autophagy lipidation machinery (e.g., ATG5, ATG7), but is independent of the ULK1/2-ATG13-RB1CC1/FIP200 preinitiation complex and thus distinct from classical autophagy. However, the underlying mechanism regulating activation of this noncanonical pathway remains unclear.…”

Section: Introductionmentioning

confidence: 99%

V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation

Florey¹,

et al. 2014

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Abbreviations: ATG, autophagy-related; Baf, bafilomycin A 1 ; CALCOCO2/NDP52, calcium binding and coiled-coil domain 2; ConA, concanamycin A; CQ, chloroquine; FYCO1, FYVE and coiled-coil domain containing 1; GFP, green fluorescent protein; LAMP1, lysosomal-associated membrane protein 1; LAP, LC3-associated phagocytosis; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MTOR, mechanistic target of rapamycin; PIK3C3/VPS34, phosphatidylinositol 3-kinase; catalytic subunit type 3; PtdIns3P, phosphatidylinositol 3-phosphate; PtdIns3K, phosphatidylinositol 3-kinase; RB1CC1/FIP200, RB1-inducible coiledcoil 1; SQSTM1/p62, sequestosome 1; TEM, transmission electron microscopy; TLR, toll-like receptor; ULK1/2, unc-51 like autophagy activating kinase 1/2; VacA, vacuolating toxin A; V-ATPase, vacuolar-type H C -ATPase.Recently a noncanonical activity of autophagy proteins has been discovered that targets lipidation of microtubuleassociated protein 1 light chain 3 (LC3) onto macroendocytic vacuoles, including macropinosomes, phagosomes, and entotic vacuoles. While this pathway is distinct from canonical autophagy, the mechanism of how these nonautophagic membranes are targeted for LC3 lipidation remains unclear. Here we present evidence that this pathway requires activity of the vacuolar-type H C -ATPase (V-ATPase) and is induced by osmotic imbalances within endolysosomal compartments. LC3 lipidation by this mechanism is induced by treatment of cells with the lysosomotropic agent chloroquine, and through exposure to the Heliobacter pylori pore-forming toxin VacA. These data add novel mechanistic insights into the regulation of noncanonical LC3 lipidation and its associated processes, including LC3-associated phagocytosis (LAP), and demonstrate that the widely and therapeutically used drug chloroquine, which is conventionally used to inhibit autophagy flux, is an inducer of LC3 lipidation.

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Noncanonical autophagy: one small step for LC3, one giant leap for immunity

Cited by 101 publications

References 49 publications

The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis

The Role of Autophagy during Group B Streptococcus Infection of Blood-Brain Barrier Endothelium

V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation

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