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Terje Johansen - One of the best experts on this subject based on the ideXlab platform.
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Selective Autophagy atg8 family proteins lir motifs and cargo receptors
Journal of Molecular Biology, 2020Co-Authors: Terje Johansen, Trond LamarkAbstract:Abstract Selective Autophagy relies on soluble or membrane-bound cargo receptors that recognize cargo and bring about autophagosome formation at the cargo. The cargo-bound receptors interact with lipidated ATG8 family proteins anchored in the membrane at the concave side of the forming autophagosome. The interaction is mediated by 15- to 20-amino-acid-long sequence motifs called LC3-interacting region (LIR) motifs that bind to the LIR docking site (LDS) of ATG8 proteins. In this review, we focus on LIR–ATG8 interactions and the soluble mammalian Selective Autophagy receptors. We discuss the roles of ATG8 family proteins as membrane scaffolds in Autophagy and the LIR–LDS interaction and how specificity for binding to GABARAP or LC3 subfamily proteins is achieved. We also discuss atypical LIR–LDS interactions and a novel LIR-independent interaction. Recently, it has become clear that several of the soluble cargo receptors are able to recruit components of the core Autophagy apparatus to aid in assembling autophagosome formation at the site of cargo sequestration. A model on phagophore recruitment and expansion on a Selective Autophagy receptor-coated cargo incorporating the latest findings is presented.
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Selective Autophagy: RNA Comes from the Vault to Regulate p62/SQSTM1
Current Biology, 2019Co-Authors: Terje JohansenAbstract:A new study shows that the oligomerization of p62/Sequestosome-1 (SQSTM1) — a Selective Autophagy receptor and signaling adapter — is regulated directly by vault RNA. This riboregulation negatively affects the aggregation state of p62 and thereby its autophagic degradation and its role as a Selective Autophagy receptor.
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regulation of Selective Autophagy the p62 sqstm1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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Regulation of Selective Autophagy: the p62/SQSTM1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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TRIM proteins regulate Autophagy: TRIM5 is a Selective Autophagy receptor mediating HIV-1 restriction
Autophagy, 2014Co-Authors: Michael A. Mandell, Terje Johansen, Tomonori Kimura, Ashish Jain, Vojo DereticAbstract:The tripartite motif protein family (TRIM) constitutes a class of immune-regulated proteins with antiviral, immune, cancer, and other properties reminiscent of those ascribed to Autophagy. We show that TRIMs have dual roles in Autophagy: as regulators and as cargo receptors. As regulators, TRIMs nucleate the core Autophagy machinery by acting as platforms that assemble ULK1 and BECN1 into a functional complex in preparation for Autophagy. TRIMs also act as novel Selective Autophagy receptors as exemplified by TRIM5/TRIM5α, a known HIV-1 restriction factor with a hitherto poorly defined mode of action. TRIM5 recognizes and targets HIV-1 for autophagic destruction. TRIM5 interactions with mammalian Atg8 proteins are required for this effector function. This establishes TRIM family members as regulators of Autophagy, explains the antiretroviral mechanism of TRIM5, and defines a new basis for Selective Autophagy.
Ivan Dikic - One of the best experts on this subject based on the ideXlab platform.
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Quantitative Phosphoproteomics of Selective Autophagy Receptors
Methods of Molecular Biology, 2019Co-Authors: Thomas Juretschke, Petra Beli, Ivan DikicAbstract:Selective Autophagy enables degradation of specific cargo such as protein aggregates or organelles and thus plays an essential role in the regulation of cellular homeostasis. Cargo specificity is achieved on the level of Autophagy receptors that concurrently bind the cargo and the autophagosomal membrane. Recent studies have demonstrated that Selective Autophagy is tightly regulated by posttranslational modifications of Autophagy receptors, in particular protein phosphorylation. Phosphorylation of Autophagy receptors by different kinases, including Tank-binding kinase (TBK1), can increase their affinity toward the cargo or autophagosomes and thereby regulate the specificity and activity of Selective Autophagy depending on the cellular condition.Here, we report an approach for quantitative analysis of phosphorylation sites on Autophagy receptors using mass spectrometry-based proteomics. In this protocol, GFP-tagged Autophagy receptors are purified based on the high-affinity binding between GFP and GFP-Trap agarose. Interaction partners and background binders are subsequently removed by washes under denaturing conditions to obtain a pure fraction of the bait protein, thereby reducing the complexity of the analyzed sample. The bait protein is then digested on-bead, and peptides are analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The described approach permits systematic identification and quantification of phosphorylation sites on Autophagy receptors and other autophagic components. In addition to phosphorylation, this protocol is suitable for investigating other posttranslational modifications, including protein ubiquitylation.
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Hitchhiking on Selective Autophagy
Nature Cell Biology, 2018Co-Authors: Christian Münch, Ivan DikicAbstract:Selective Autophagy is important for controlled degradation of cellular components. However, a Selective autophagic degradation mechanism for ribosomes in mammals has remained unclear. A study now describes non-Selective and Selective ribosome degradation and a significant role for ‘bystander’ non-Selective Autophagy.
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ubiquitin dependent and independent signals in Selective Autophagy
Trends in Cell Biology, 2016Co-Authors: Aliaksandr Khaminets, Christian Behl, Ivan DikicAbstract:Selective Autophagy regulates the abundance of specific cellular components via a specialized arsenal of factors, termed Autophagy receptors, that target protein complexes, aggregates, and whole organelles into lysosomes. Autophagy receptors bind to LC3/GABARAP proteins on phagophore and autophagosome membranes, and recognize signals on cargoes to deliver them to Autophagy. Ubiquitin (Ub), a well-known signal for the degradation of polypeptides in the proteasome, also plays an important role in the recognition of cargoes destined for Selective Autophagy. In addition, a variety of cargoes are committed to Selective Autophagy pathways by Ub-independent mechanisms employing protein–protein interaction motifs, Ub-like modifiers, and sugar- or lipid-based signals. In this article we summarize Ub-dependent and independent Selective Autophagy pathways, and discuss regulatory mechanisms and challenges for future studies.
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cargo recognition and trafficking in Selective Autophagy
Nature Cell Biology, 2014Co-Authors: Alexandra Stolz, Andreas Ernst, Ivan DikicAbstract:The degradation of dysfunctional proteins and organelles by Autophagy is important for cell viability. Dikic and co-authors discuss how cargo selection is achieved during Selective Autophagy and how the processes involved in cargo delivery are related to membrane trafficking pathways.
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Cargo recognition and trafficking in Selective Autophagy
Nature Cell Biology, 2014Co-Authors: Alexandra Stolz, Andreas Ernst, Ivan DikicAbstract:Selective Autophagy is a quality control pathway through which cellular components are sequestered into double-membrane vesicles and delivered to specific intracellular compartments. This process requires Autophagy receptors that link cargo to growing autophagosomal membranes. Selective Autophagy is also implicated in various membrane trafficking events. Here we discuss the current view on how cargo selection and transport are achieved during Selective Autophagy, and point out molecular mechanisms that are congruent between Autophagy and vesicle trafficking pathways.
Trond Lamark - One of the best experts on this subject based on the ideXlab platform.
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Selective Autophagy atg8 family proteins lir motifs and cargo receptors
Journal of Molecular Biology, 2020Co-Authors: Terje Johansen, Trond LamarkAbstract:Abstract Selective Autophagy relies on soluble or membrane-bound cargo receptors that recognize cargo and bring about autophagosome formation at the cargo. The cargo-bound receptors interact with lipidated ATG8 family proteins anchored in the membrane at the concave side of the forming autophagosome. The interaction is mediated by 15- to 20-amino-acid-long sequence motifs called LC3-interacting region (LIR) motifs that bind to the LIR docking site (LDS) of ATG8 proteins. In this review, we focus on LIR–ATG8 interactions and the soluble mammalian Selective Autophagy receptors. We discuss the roles of ATG8 family proteins as membrane scaffolds in Autophagy and the LIR–LDS interaction and how specificity for binding to GABARAP or LC3 subfamily proteins is achieved. We also discuss atypical LIR–LDS interactions and a novel LIR-independent interaction. Recently, it has become clear that several of the soluble cargo receptors are able to recruit components of the core Autophagy apparatus to aid in assembling autophagosome formation at the site of cargo sequestration. A model on phagophore recruitment and expansion on a Selective Autophagy receptor-coated cargo incorporating the latest findings is presented.
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regulation of Selective Autophagy the p62 sqstm1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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Regulation of Selective Autophagy: the p62/SQSTM1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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the lir motif crucial for Selective Autophagy
Journal of Cell Science, 2013Co-Authors: Asa Birna Birgisdottir, Trond Lamark, Terje JohansenAbstract:(Macro)Autophagy is a fundamental degradation process for macromolecules and organelles of vital importance for cell and tissue homeostasis. Autophagy research has gained a strong momentum in recent years because of its relevance to cancer, neurodegenerative diseases, muscular dystrophy, lipid storage disorders, development, ageing and innate immunity. Autophagy has traditionally been thought of as a bulk degradation process that is mobilized upon nutritional starvation to replenish the cell with building blocks and keep up with the energy demand. This view has recently changed dramatically following an array of papers describing various forms of Selective Autophagy. A main driving force has been the discovery of specific Autophagy receptors that sequester cargo into forming autophagosomes (phagophores). At the heart of this selectivity lies the LC3-interacting region (LIR) motif, which ensures the targeting of Autophagy receptors to LC3 (or other ATG8 family proteins) anchored in the phagophore membrane. LIR-containing proteins include cargo receptors, members of the basal Autophagy apparatus, proteins associated with vesicles and of their transport, Rab GTPase-activating proteins (GAPs) and specific signaling proteins that are degraded by Selective Autophagy. Here, we comment on these new insights and focus on the interactions of LIR-containing proteins with members of the ATG8 protein family.
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The LIR motif – crucial for Selective Autophagy
Journal of Cell Science, 2013Co-Authors: Asa Birna Birgisdottir, Trond Lamark, Terje JohansenAbstract:(Macro)Autophagy is a fundamental degradation process for macromolecules and organelles of vital importance for cell and tissue homeostasis. Autophagy research has gained a strong momentum in recent years because of its relevance to cancer, neurodegenerative diseases, muscular dystrophy, lipid storage disorders, development, ageing and innate immunity. Autophagy has traditionally been thought of as a bulk degradation process that is mobilized upon nutritional starvation to replenish the cell with building blocks and keep up with the energy demand. This view has recently changed dramatically following an array of papers describing various forms of Selective Autophagy. A main driving force has been the discovery of specific Autophagy receptors that sequester cargo into forming autophagosomes (phagophores). At the heart of this selectivity lies the LC3-interacting region (LIR) motif, which ensures the targeting of Autophagy receptors to LC3 (or other ATG8 family proteins) anchored in the phagophore membrane. LIR-containing proteins include cargo receptors, members of the basal Autophagy apparatus, proteins associated with vesicles and of their transport, Rab GTPase-activating proteins (GAPs) and specific signaling proteins that are degraded by Selective Autophagy. Here, we comment on these new insights and focus on the interactions of LIR-containing proteins with members of the ATG8 protein family.
Vladimir Kirkin - One of the best experts on this subject based on the ideXlab platform.
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Selective Autophagy receptors in neuronal health and disease.
Journal of Molecular Biology, 2019Co-Authors: Owen Conway, Hafize Aysin Akpinar, Vladimir V. Rogov, Vladimir KirkinAbstract:Abstract Neurons are electrically excitable, post-mitotic cells that perform sensory, relaying, and motor functions. Because of their unique morphological and functional specialization, cells of this type are sensitive to the stress caused by accumulation of misfolded proteins or damaged organelles. Autophagy is the fundamental mechanism that ensures sequestration of cytosolic material and its subsequent degradation in lysosomes of eukaryotic cells, thereby providing cell-autonomous nutrients and removing harmful cargos. Strikingly, mice and flies lacking functional Autophagy develop early-onset progressive neurodegeneration. Like in human neurodegenerative diseases (NDDs) – Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, Huntingtin’s disease, and amyotrophic lateral sclerosis – characteristic protein aggregates observed in Autophagy-deficient neurons in the animal models are indicators of the ongoing neuronal pathology. A number of Selective Autophagy receptors (SARs) have been characterized that interact both with the cargo and components of the autophagic machinery, thus providing the molecular basis for Selective degradation of sizable cytosolic components. Interference with Autophagy in experimental models, but also during the pathological vagaries in neurons, will thus have far-reaching consequences for a range of Selective Autophagy pathways critical for the normal functioning of the nervous system. Here, we review the key principles behind the Selective Autophagy and discuss how the SARs may be involved in the pathogenesis of NDDs. Using recently published examples, we also examine the emerging role of less well studied Selective Autophagy pathways in neuronal health and disease. We conclude by discussing targeting Selective Autophagy as an emerging therapeutic modality in NDDs.
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History of the Selective Autophagy Research: How Did It Begin and Where Does It Stand Today?
Journal of Molecular Biology, 2019Co-Authors: Vladimir KirkinAbstract:Abstract Autophagy, self-eating, is a pivotal catabolic mechanism that ensures homeostasis and survival of the cell in the face of stressors as different as starvation, infection, or protein misfolding. The importance of the research in this field was recognized by the general public after the Nobel Prize for Physiology or Medicine was awarded in 2016 to Yoshinori Ohsumi for discoveries of the mechanisms of Autophagy using yeast as a model organism. One of the seminal findings of Ohsumi was on the role ubiquitin-like proteins (UBLs)—Atg5, Atg12, and Atg8—play in the formation of the double-membrane vesicle autophagosome, which is the functional unit of Autophagy. Subsequent work by several groups demonstrated that, like the founding member of the UBL family ubiquitin, these small but versatile protein and lipid modifiers interact with a plethora of proteins, which either directly regulate autophagosome formation, for example, components of the Atg1/ULK1 complex, or are involved in cargo recognition, for example, Atg19 and p62/SQSTM1. By tethering the cargo to the UBLs present on the forming autophagosome, the latter proteins were proposed to effectively act as Selective Autophagy receptors. The discovery of the Selective Autophagy receptors brought a breakthrough in the Autophagy field, supplying the mechanistic underpinning for the formation of an autophagosome Selectively around the cytosolic cargo, that is, a protein aggregate, a mitochondrion, or a cytosolic bacterium. In this historical overview, I highlight key steps that the research into Selective Autophagy has been taking over the past 20 years. I comment on their significance and discuss current challenges in developing more detailed knowledge of the mechanisms of Selective Autophagy. I will conclude by introducing the new directions that this dynamic research field is taking into its third decade.
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Caging the Elephant: Selective Autophagy Tackles Giant Intracellular Protein Crystals
Molecular Cell, 2015Co-Authors: Sabrina Habisov, Vladimir KirkinAbstract:In this issue of Molecular Cell, Tsutsui et al. (2015) show that in vivo protein crystallization may come in handy not only when solving the structure of a protein, but also when studying molecular mechanisms of Selective Autophagy.
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interactions between Autophagy receptors and ubiquitin like proteins form the molecular basis for Selective Autophagy
Molecular Cell, 2014Co-Authors: Vladimir V. Rogov, Terje Johansen, Volker Dotsch, Vladimir KirkinAbstract:Selective Autophagy ensures recognition and removal of various cytosolic cargos. Hence, aggregated proteins, damaged organelles, or pathogens are enclosed into the double-membrane vesicle, the autophagosome, and delivered to the lysosome for degradation. This process is mediated by Selective Autophagy receptors, such as p62/SQSTM1. These proteins recognize autophagic cargo and, via binding to small ubiquitin-like modifiers (UBLs)—Atg8/LC3/GABARAPs and ATG5—mediate formation of Selective autophagosomes. Recently, it was found that UBLs can directly engage the autophagosome nucleation machinery. Here, we review recent findings on Selective Autophagy and propose a model for Selective autophagosome formation in close proximity to cargo.
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Selective Autophagy in cancer development and therapy
Cancer Research, 2010Co-Authors: Ivan Dikic, Terje Johansen, Vladimir KirkinAbstract:Like other cells in the body, tumor cells depend on the evolutionarily conserved Autophagy pathway to survive starvation and stress. Simultaneously, Autophagy represents an important tumor-suppressive mechanism. Recent studies have shed new light on this apparent discrepancy and revealed mechanisms by which Autophagy can modulate different stages of cancer development. The molecular basis of selectivity in Autophagy employs specific receptor molecules, such as p62/SQSTM1, which are able to link Autophagy targets and autophagosomal membranes. We discuss the emerging principles of Selective Autophagy in cancer pathogenesis and treatment. Cancer Res; 70(9); 3431–4. ©2010 AACR.
Steingrim Svenning - One of the best experts on this subject based on the ideXlab platform.
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Regulation of Selective Autophagy: the p62/SQSTM1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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regulation of Selective Autophagy the p62 sqstm1 paradigm
Essays in Biochemistry, 2017Co-Authors: Trond Lamark, Steingrim Svenning, Terje JohansenAbstract:In Selective Autophagy, cytoplasmic components are selected and tagged before being sequestered into an autophagosome by means of Selective Autophagy receptors such as p62/SQSTM1. In this review, we discuss how Selective Autophagy is regulated. An important level of regulation is the selection of proteins or organelles for degradation. Components selected for degradation are tagged, often with ubiquitin, to facilitate recognition by Autophagy receptors. Another level of regulation is represented by the Autophagy receptors themselves. For p62, its ability to co-aggregate with ubiquitinated substrates is strongly induced by post-translational modifications (PTMs). The transcription of p62 is also markedly increased during conditions in which Selective Autophagy substrates accumulate. For other Autophagy receptors, the LC3-interacting region (LIR) motif is regulated by PTMs, inhibiting or stimulating the interaction with ATG8 family proteins. ATG8 proteins are also regulated by PTMs. Regulation of the capacity of the core Autophagy machinery also affects Selective Autophagy. Importantly, Autophagy receptors can induce local recruitment and activation of ULK1/2 and PI3KC3 complexes at the site of cargo sequestration.
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Selective Autophagy.
Essays in biochemistry, 2013Co-Authors: Steingrim Svenning, Terje JohansenAbstract: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).
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plant nbr1 is a Selective Autophagy substrate and a functional hybrid of the mammalian autophagic adapters nbr1 and p62 sqstm1
Autophagy, 2011Co-Authors: Steingrim Svenning, Trond Lamark, Kirsten Krause, Terje JohansenAbstract:(Macro)Autophagy encompasses both an unSelective, bulk degradation of cytoplasmic contents as well as Selective Autophagy of damaged organelles, intracellular microbes, protein aggregates, cellular structures and specific soluble proteins. Selective Autophagy is mediated by autophagic adapters, like p62/SQSTM1 and NBR1. p62 and NBR1 are themselves Selective Autophagy substrates, but they also act as cargo receptors for degradation of other substrates. Surprisingly, we found that homologs of NBR1 are distributed throughout the eukaryotic kingdom, while p62 is confined to the metazoans. As a representative of all organisms having only an NBR1 homolog we studied Arabidopsis thaliana NBR1 (AtNBR1) in more detail. AtNBR1 is more similar to mammalian NBR1 than to p62 in domain architecture and amino acid sequence. However, similar to p62, AtNBR1 homo-polymerizes via the PB1 domain. Hence, AtNBR1 has hybrid properties of mammalian NBR1 and p62. AtNBR1 has 2 UBA domains, but only the C-terminal UBA domain bound u...
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Plant NBR1 is a Selective Autophagy substrate and a functional hybrid of the mammalian autophagic adapters NBR1 and p62/SQSTM1.
Autophagy, 2011Co-Authors: Steingrim Svenning, Trond Lamark, Kirsten Krause, Terje JohansenAbstract:(Macro)Autophagy encompasses both an unSelective, bulk degradation of cytoplasmic contents as well as Selective Autophagy of damaged organelles, intracellular microbes, protein aggregates, cellular structures and specific soluble proteins. Selective Autophagy is mediated by autophagic adapters, like p62/SQSTM1 and NBR1. p62 and NBR1 are themselves Selective Autophagy substrates, but they also act as cargo receptors for degradation of other substrates. Surprisingly, we found that homologs of NBR1 are distributed throughout the eukaryotic kingdom, while p62 is confined to the metazoans. As a representative of all organisms having only an NBR1 homolog we studied Arabidopsis thaliana NBR1 (AtNBR1) in more detail. AtNBR1 is more similar to mammalian NBR1 than to p62 in domain architecture and amino acid sequence. However, similar to p62, AtNBR1 homo-polymerizes via the PB1 domain. Hence, AtNBR1 has hybrid properties of mammalian NBR1 and p62. AtNBR1 has 2 UBA domains, but only the C-terminal UBA domain bound u...
