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Endosome-mediated autophagy: an unconventional MIIC-driven autophagic pathway operational in dendritic cells.

ABSTRACT: Activation of TLR signaling has been shown to induce autophagy in antigen-presenting cells (APCs). Using high-resolution microscopy approaches, we show that in LPS-stimulated dendritic cells (DCs), autophagosomes emerge from MHC class II compartments (MIICs) and harbor both the molecular machinery for antigen processing and the autophagosome markers LC3 and ATG16L1. This ENdosome-Mediated Autophagy (ENMA) appears to be the major type of autophagy in DCs, as similar structures were observed upon established autophagy-inducing conditions (nutrient deprivation, rapamycin) and under basal conditions in the presence of bafilomycin A1. Autophagosome formation was not significantly affected in DCs expressing ATG4B (C74A) mutant and atg4b (-/-) bone marrow DCs, but the degradation of the autophagy substrate SQSTM1/p62 was largely impaired. Furthermore, we demonstrate that the previously described DC aggresome-like LPS-induced structures (DALIS) contain vesicular membranes, and in addition to SQSTM1 and ubiquitin, they are positive for LC3. LC3 localization on DALIS is independent of its lipidation. MIIC-driven autophagosomes preferentially engulf the LPS-induced SQSTM1-positive DALIS, which become later degraded in autolysosomes. DALIS-associated membranes also contain ATG16L1, ATG9 and the Q-SNARE VTI1B, suggesting that they may represent (at least in part) a membrane reservoir for autophagosome expansion. We propose that ENMA constitutes an unconventional, APC-specific type of autophagy, which mediates the processing and presentation of cytosolic antigens by MHC class II machinery, and/or the selective clearance of toxic by-products of elevated ROS/RNS production in activated DCs, thereby promoting their survival.

SUBMITTER: Kondylis V

PROVIDER: S-EPMC3672296 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Endosome-mediated autophagy: an unconventional MIIC-driven autophagic pathway operational in dendritic cells.

Kondylis Vangelis V van Nispen Tot Pannerden Hezder E HE van Dijk Suzanne S Ten Broeke Toine T Wubbolts Richard R Geerts Willie J WJ Seinen Cor C Mutis Tuna T Heijnen Harry F G HF

Autophagy 20130312 6

Activation of TLR signaling has been shown to induce autophagy in antigen-presenting cells (APCs). Using high-resolution microscopy approaches, we show that in LPS-stimulated dendritic cells (DCs), autophagosomes emerge from MHC class II compartments (MIICs) and harbor both the molecular machinery for antigen processing and the autophagosome markers LC3 and ATG16L1. This ENdosome-Mediated Autophagy (ENMA) appears to be the major type of autophagy in DCs, as similar structures were observed upon ...[more]

PMID: 23481895

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Dataset Information

Endosome-mediated autophagy: an unconventional MIIC-driven autophagic pathway operational in dendritic cells.

Publications

Endosome-mediated autophagy: an unconventional MIIC-driven autophagic pathway operational in dendritic cells.

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