Selective autophagy

2013 ◽  
Vol 55 ◽  
pp. 79-92 ◽  
Author(s):  
Steingrim Svenning ◽  
Terje Johansen
Keyword(s):  
Light Chain ◽  
Bacterial Pathogens ◽  
Protein Aggregates ◽  
Degradation Pathway ◽  
Intracellular Bacteria ◽  
Related Protein ◽  
Lysosomal Degradation ◽  
Selective Autophagy

During the last decade it has become evident that autophagy is not simply a non-selective bulk degradation pathway for intracellular components. On the contrary, the discovery and characterization of autophagy receptors which target specific cargo for lysosomal degradation by interaction with ATG8 (autophagy-related protein 8)/LC3 (light-chain 3) has accelerated our understanding of selective autophagy. A number of autophagy receptors have been identified which specifically mediate the selective autophagosomal degradation of a variety of cargoes including protein aggregates, signalling complexes, midbody rings, mitochondria and bacterial pathogens. In the present chapter, we discuss these autophagy receptors, their binding to ATG8/LC3 proteins and how they act in ubiquitin-mediated selective autophagy of intracellular bacteria (xenophagy) and protein aggregates (aggrephagy).

scholarly journals Broad and Complex Roles of NBR1-Mediated Selective Autophagy in Plant Stress Responses

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2562
Author(s):  
Yan Zhang ◽  
Zhixiang Chen
Keyword(s):  
Stress Responses ◽  
Mammalian Cells ◽  
Plant Stress ◽  
Protein Aggregates ◽  
Degradation Pathway ◽  
Plant Responses ◽  
Stress Memory ◽  
Selective Autophagy ◽  
Cargo Proteins ◽  
Plant Stress Responses

Selective autophagy is a highly regulated degradation pathway for the removal of specific damaged or unwanted cellular components and organelles such as protein aggregates. Cargo selectivity in selective autophagy relies on the action of cargo receptors and adaptors. In mammalian cells, two structurally related proteins p62 and NBR1 act as cargo receptors for selective autophagy of ubiquitinated proteins including aggregation-prone proteins in aggrephagy. Plant NBR1 is the structural and functional homolog of mammalian p62 and NBR1. Since its first reports almost ten years ago, plant NBR1 has been well established to function as a cargo receptor for selective autophagy of stress-induced protein aggregates and play an important role in plant responses to a broad spectrum of stress conditions including heat, salt and drought. Over the past several years, important progress has been made in the discovery of specific cargo proteins of plant NBR1 and their roles in the regulation of plant heat stress memory, plant-viral interaction and special protein secretion. There is also new evidence for a possible role of NBR1 in stress-induced pexophagy, sulfur nutrient responses and abscisic acid signaling. In this review, we summarize these progresses and discuss the potential significance of NBR1-mediated selective autophagy in broad plant responses to both biotic and abiotic stresses.

scholarly journals In situ characterization of protein aggregates in human tissues affected by light chain amyloidosis: a FTIR microspectroscopy study

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Diletta Ami ◽  
Francesca Lavatelli ◽  
Paola Rognoni ◽  
Giovanni Palladini ◽  
Sara Raimondi ◽  
...  
Keyword(s):  
Light Chain ◽  
Protein Aggregates ◽  
Human Tissues ◽  
In Situ Characterization ◽  
Light Chain Amyloidosis ◽  
Ftir Microspectroscopy

scholarly journals Monitoring LC3- or GABARAP-positive autophagic membranes using modified RavZ-based probes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sang-Won Park ◽  
Pureum Jeon ◽  
Yong-Woo Jun ◽  
Ju-Hui Park ◽  
Seung-Hwan Lee ◽  
...  
Keyword(s):  
Protein Binding ◽  
Catalytic Domain ◽  
Degradation Pathway ◽  
Host Cells ◽  
Membrane Association ◽  
Membrane Targeting ◽  
Related Protein ◽  
Lysosomal Degradation ◽  
Hydrophobic Domain ◽  
Survival Mechanisms

Abstract Xenophagy is a selective lysosomal degradation pathway for invading pathogens in host cells. However, invading bacteria also develop survival mechanisms to inhibit host autophagy. RavZ is a protein secreted by Legionella that irreversibly delipidates mammalian autophagy-related protein 8 (mATG8) on autophagic membranes in host cells via efficient autophagic membrane targeting. In this study, we leveraged the autophagic membrane-targeting mechanism of RavZ and generated a new autophagosome probe by replacing the catalytic domain of RavZ with GFP. This probe is efficiently localized to mATG8-positive autophagic membranes via a synergistic combination between mATG8 protein-binding mediated by the LC3-interacting region (LIR) motifs and phosphoinositide-3-phosphate (PI3P) binding mediated by the membrane-targeting (MT) domain. Furthermore, the membrane association activity of this new probe with an MT domain was more efficient than that of probes with a hydrophobic domain that were previously used in LIR-based autophagosome sensors. Finally, by substituting the LIR motifs of RavZ with selective LIR motifs from Fyco1 or ULK2, we developed new probes for detecting LC3A/B- or GABARAP subfamily-positive autophagic membranes, respectively. We propose that these new RavZ-based sensors will be useful for monitoring and studying the function of mATG8-positive autophagic membranes in different cellular contexts for autophagy research.

Abstract 4: Enhancing the Ability of Macrophages to Orchestrate Selective Autophagy and Lysosomal Biogenesis Protects Against Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Ismail Sergin ◽  
Somashubhra Bhattacharya ◽  
Xiangyu Zhang ◽  
Trent D Evans ◽  
Babak Dehestani ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Membrane Integrity ◽  
Protein Aggregates ◽  
Plaque Burden ◽  
Inflammasome Activation ◽  
Lysosomal Degradation ◽  
Cytoplasmic Inclusions ◽  
Selective Autophagy ◽  
Mechanistic Basis

The autophagy-lysosome system is a catabolic cellular mechanism that degrades dysfunctional proteins and organelles. The pro-atherogenic phenotype of mice with macrophage-specific autophagy deficiency (ATG5-/-) confirm the importance of this degradation system in the pathogenesis of atherosclerosis. The mechanistic basis appears to involve a two-step process in macrophages: the development of lysosomal dysfunction/membrane integrity by atherogenic lipids followed by an inability of lysosomes to handle and degrade cargo supplied by autophagy. A prominent sequelae of such blockage is the accumulation of cytoplasmic inclusions composed of polyubiquitinated protein aggregates and organelles which are normally targeted for selective autophagy by the protein chaperone p62. In order to stimulate the degradative capacity of macrophages, we developed mice with macrophage-specific overexpression of TFEB, a master transcriptional activator of both autophagy and lysosomal biogenesis. Macrophage TFEB ameliorated several deleterious effects of atherogenic lipids, namely the blunting of inflammasome activation, enhancing cholesterol efflux, accelerating the degradation of protein aggregates, and decreasing apoptosis. In vivo, macrophage TFEB overexpression reduced both plaque burden and plaque complexity in pro-atherogenic ApoE-/- mice fed a Western diet. Interestingly, TFEB’s atheroprotective effects were not only abrogated in the background of macrophage autophagy deficiency (ATG5-/-) but also in the background of p62-deficiency (p62-/-) suggesting the critical importance of selective autophagy and degradation of p62-enriched protein aggregates. Taken together, these data support the induction of a holistic pro-degradative response in macrophages (i.e. selective autophagy followed by lysosomal degradation) as a viable therapeutic strategy in atherosclerosis.

scholarly journals Decoding the consecutive lysosomal degradation of 3-O-sulfate containing heparan sulfate by Arylsulfatase G (ARSG)

2021 ◽  
Author(s):  
Björn Kowalewski ◽  
Heike Lange ◽  
Sabrina Galle ◽  
Thomas Dierks ◽  
Torben Lübke ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Fluorescent Dyes ◽  
Usher Syndrome ◽  
Degradation Pathway ◽  
Reversed Phase ◽  
Lysosomal Degradation ◽  
Type Iv ◽  
Derivatives Of ◽  
Usher Syndrome Type

The lysosomal degradation of heparan sulfate is mediated by the concerted action of nine different enzymes. Within this degradation pathway, Arylsulfatase G (ARSG) is critical for removing 3-O-sulfate from glucosamine, and mutations in ARSG are causative for Usher syndrome type IV. We developed a specific ARSG enzyme assay using sulfated monosaccharide substrates, which reflect derivatives of its natural substrates. These sulfated compounds were incubated with ARSG, and resulting products were analyzed by reversed-phase HPLC after chemical addition of the fluorescent dyes 2-aminoacridone or 2-aminobenzoic acid, respectively. We applied the assay to further characterize ARSG regarding its hydrolytic specificity against 3-O-sulfated monosaccharides containing additional sulfate-groups and N-acetylation. The application of recombinant ARSG and cells overexpressing ARSG as well as isolated lysosomes from wildtype and Arsg knockout mice validated the utility of our assay. We further exploited the assay to determine the sequential action of the different sulfatases involved in the lysosomal catabolism of 3-O-sulfated glucosamine residues of heparan sulfate. Our results confirm and extend the characterization of the substrate specificity of ARSG and help to determine the sequential order of the lysosomal catabolic breakdown of (3-O-)sulfated heparan sulfate.

scholarly journals Purification and Characterization of Recombinant Human Parathyroid Hormone-related Protein

1989 ◽  
Vol 264 (25) ◽  
pp. 14806-14811
Author(s):  
R G Hammonds ◽  
P McKay ◽  
G A Winslow ◽  
H Diefenbach-Jagger ◽  
V Grill ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Human Parathyroid Hormone ◽  
Purification And Characterization ◽  
Parathyroid Hormone Related Protein
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