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Query: UMLS:C0276640 (
TEM
)
20,729
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Representatives of all major metazoan lineages form biominerals. The molecular mechanisms that underlie this widespread and evolutionarily ancient ability are gradually being revealed for some lineages. However, until a wider range of metazoan biomineralization strategies are understood, the true diversity, and therefore the evolutionary origins of this process, will remain unknown. We have previously shown that the coralline demosponge, Astrosclera willeyana, in some way employs its endobiotic bacterial community to form its highly calcified skeleton. Here, using in situ hybridization and immunohistochemistry, we show that an ortholog of ATG8 (most likely a
GABARAPL2
/
GATE-16
ortholog) is expressed in cells that construct the individual skeletal elements of the sponge. In
TEM
sections sponge cells can be observed to contain extensive populations of bacteria, and frequently possesses double-membrane structures which we interpret to be autophagosomes. In combination with our previous work, these findings support the hypothesis that the host sponge actively degrades a proportion of its bacterial community using an autophagy pathway, and uses the prokaryotic organic remains as a framework upon which calcification of the sponge skeleton is initiated.
...
PMID:Symbiophagy and biomineralization in the "living fossil" Astrosclera willeyana. 2434 43
Macroautophagy/autophagy is a cellular degradation pathway that delivers cytoplasmic material to lysosomes via double-membrane organelles called autophagosomes. Lipidation of ubiquitin-like LC3/GABARAP proteins on the autophagosome membrane is important for autophagy. The cysteine protease ATG4 executes 2 LC3/GABARAP processing events: priming of newly synthesized pro-LC3/GABARAP to enable subsequent lipidation, and delipidation/deconjugation of lipidated LC3/GABARAP (the exact purpose of which is unclear in mammals). Four ATG4 isoforms (ATG4A to ATG4D) exist in mammals; however, the functional redundancy of these proteins in cells is poorly understood. Here we show that human HAP1 and HeLa cells lacking ATG4B exhibit a severe but incomplete defect in LC3/GABARAP processing and autophagy. By further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to residual priming activity, which is sufficient to enable lipidation of endogenous GABARAPL1 on autophagic structures. We also demonstrate that expressing high levels of pre-primed LC3B in ATG4-deficient cells can rescue a defect in autophagic degradation of the cargo receptor SQSTM1/p62, suggesting that delipidation by human ATG4 is not essential for autophagosome formation and fusion with lysosomes. Overall, our study provides a comprehensive characterization of ATG4 isoform function during autophagy in human cells. Abbreviations: Atg: autophagy-related; baf A1: bafilomycin A
1;
CASP3: caspase 3; CLEM: correlative light and electron microscopy; CMV: cytomegalovirus; CRISPR: clustered regularly interspaced short palindromic repeats; DKO: double knockout; EGFP: enhanced green fluorescent protein; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor-associated protein like 1;
GABARAPL2
: GABA type A receptor-associated protein like 2; GFP: green fluorescent protein; HB: homogenization buffer; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LIR: LC3 interacting region; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MFN2: mitofusin 2; N.A.: numerical aperture; NEM: N-ethylmaleimide; PDHA1: pyruvate dehydrogenase E1 alpha 1 subunit; PLD: phospholipase D; PE: phosphatidylethanolamine; RLUC: Renilla luciferase; SQSTM1: sequestosome 1;
TEM
: transmission electron microscopy; TKO: triple knockout; ULK1: unc-51 like autophagy activating kinase 1; VCL: vinculin; WT: wild-type.
...
PMID:Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells. 3066 29
