Crucial role for autophagy in degranulation of mast cells

Ushio, Hiroko; Ueno, Takashi; Kojima, Yuko; Komatsu, Masaaki; Tanaka, Satoshi; Yamamoto, Akira; Ichimura, Yoshinobu; Ezaki, Junji; Nishida, Keigo; Komazawa-Sakon, Sachiko; Niyonsaba, François; Ishii, Tetsuro; Yanagawa, Toru; Kominami, Eiki; Ogawa, Hideoki; Okumura, Ko; Nakano, Hiroyasu

doi:10.1016/j.jaci.2010.12.1078

Cited by 121 publications

(107 citation statements)

References 36 publications

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“…Another intriguing question is how caspase-3, a protein that is devoid of an endoplasmic reticulum localization signal peptide, is transported into the secretory granule compartment of mast cells. In a recent report, a role of autophagy in mast cell degranulation processes was suggested (27), and it was also shown that LC3-II, an autophagy-associated compound that is normally not present within organelles of the secretory pathway, was localized in mast cell granules (27). Based on these findings, it could thus be speculated that autophagy may have a bearing on mast cell granules and that, possibly, cytosolic compounds may enter the secretory granule compartment through autophagy.…”

Section: Discussionmentioning

confidence: 99%

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Garcia-Faroldi

Melo

Rönnberg

et al. 2013

The Journal of Immunology

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Caspase-3 is a main executioner of apoptotic cell death. The general notion is that, in viable cells, caspase-3 is found as a cytosolic inactive proenzyme and that caspase-3 activation is largely confined to processes associated with cell death. In this study, we challenge this notion by showing that enzymatically active caspase-3 is stored in viable mast cells. The enzymatically active caspase-3 was undetectable in the cytosol of viable cells, but was recovered in subcellular fractions containing secretory granule-localized proteases. Moreover, active caspase-3 was rapidly released into the cytosolic compartment after permeabilization of the secretory granules. Using a cell-permeable substrate for caspase-3, the presence of active caspase-3–like activity in granule-like compartments close to the plasma membrane was demonstrated. Moreover, it was shown that mast cell activation caused release of the caspase-3 to the cell exterior. During the course of mast cell differentiation from bone marrow cells, procaspase-3 was present in cells of all stages of maturation. In contrast, active caspase-3 was undetectable in bone marrow precursor cells, but increased progressively during the process of mast cell maturation, its accumulation coinciding with that of a mast cell–specific secretory granule marker, mouse mast cell protease 6. Together, the current study suggests that active caspase-3 can be stored within secretory compartments of viable mast cells.

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Section: Discussionmentioning

confidence: 99%

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Garcia-Faroldi

Melo

Rönnberg

et al. 2013

The Journal of Immunology

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“…Third, it is uncertain whether the autophagosomes are transported directly to the cell surface for secretion or whether they fuse with endocytic pathway components such as the multi-vesicular body (MVB). Because studies suggest that the exocytosis of MVBs can mediate the transport of intracellular cargo directly to the cell surface, the latter model seems the most plausible 134 . Indeed, early evidence suggests that the autophagy machinery may intersect with the endosomal sorting complexes required for transport (ESCRT) machinery to promote multiple MVB-associated functions, including exocytosis.…”

Section: Box 2 | Autophagy and Secretionmentioning

confidence: 99%

Autophagy at the crossroads of catabolism and anabolism

Kaur

Debnath

2015

Nat Rev Mol Cell Biol

842

801

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“…Alternatively, some autophagosomes can be directed to the plasma membrane and fuse with this membrane, thereby promoting the release of their content into the environment for exophagy. 8,9 A potential role of autophagy during the differentiation of protozoan parasites is emerging. [10][11][12][13] A notable example has been illustrated for Trypanosoma brucei differentiation, in which a rapid turnover of glycosomes is facilitated by selective autophagy.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the ATG8-conjugation system in 2Plasmodiumspecies with special focus on the liver stage

et al. 2013

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Keywords: malaria, Plasmodium liver forms, cellular differentiation, autophagy-related genes, ATG8, apicoplast Abbreviations: ACP, acyl carrier protein; ATG, autophagy-related (gene); ATG, autophagy-related (protein); GABARAP, GABA(A) receptor-associated protein; GFP, green fluorescent protein; IEM, immunoelectron microscopy; IFA, immunofluorescence assays; LC3, microtubule-associated protein 1 light chain 3; mCherry, mCherry red fluorescent protein; ORF, open reading frame; PbATG3, Plasmodium berghei ATG3; PbATG7, Plasmodium berghei ATG7; PbATG8, Plasmodium berghei ATG8; PGK, phosphoglycerate kinase; PDM, product of the differences from the mean; PE, phosphatidylethanolamine; PfATG8, Plasmodium falciparum ATG8; p.i., post-infection; prApe1, precursor form of aminopeptidase I; PtdIns3P, phosphatidylinositol 3-phosphate; PV, parasitophorous vacuolePlasmodium parasites successfully colonize different habitats within mammals and mosquitoes, and adaptation to various environments is accompanied by changes in their organelle composition and size. Previously, we observed that during hepatocyte infection, Plasmodium discards organelles involved in invasion and expands those implicated in biosynthetic pathways. We hypothesized that this process is regulated by autophagy. Plasmodium spp. possess a rudimentary set of known autophagy-related proteins that includes the ortholog of yeast atg8. in this study, we analyzed the activity of the aTG8-conjugation pathway over the course of the lifecycle of Plasmodium falciparum and during the liver stage of Plasmodium berghei. We engineered a transgenic P. falciparum strain expressing mcherry-PfaTG8. These transgenic parasites expressed mcherry-PfaTG8 in human hepatocytes and erythrocytes, and in the midgut and salivary glands of Anopheles mosquitoes. in all observed stages, mcherry-PfaTG8 was localized to tubular structures. Our eM and colocalization studies done in P. berghei showed the association of PbaTG8 on the limiting membranes of the endosymbiont-derived plastid-like organelle known as the apicoplast. interestingly, during parasite replication in hepatocytes, the association of PbaTG8 with the apicoplast increases as this organelle expands in size. PbATG3, PbATG7 and PbATG8 are cotranscribed in all parasitic stages. Molecular analysis of PbaTG8 and PbaTG3 revealed a novel mechanism of interaction compared with that observed for other orthologs. This is further supported by the inability of Plasmodium aTG8 to functionally complement atg8Δ yeast or localize to autophagosomes in starved mammalian cells. altogether, these data suggests a unique role for the aTG8-conjugation system in Plasmodium parasites.

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Crucial role for autophagy in degranulation of mast cells

Cited by 121 publications

References 36 publications

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Active Caspase-3 Is Stored within Secretory Compartments of Viable Mast Cells

Autophagy at the crossroads of catabolism and anabolism

Characterization of the ATG8-conjugation system in 2Plasmodiumspecies with special focus on the liver stage

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