scholarly journals The role of Tecpr1 in selective autophagy as a cargo receptor

Autophagy ◽  
2011 ◽  
Vol 7 (11) ◽  
pp. 1389-1391 ◽  
Author(s):  
Michinaga Ogawa ◽  
Chihiro Sasakawa
Keyword(s):  
Selective Autophagy ◽  
Cargo Receptor

scholarly journals NBR1 directly promotes the formation of p62 – ubiquitin condensates via its PB1 and UBA domains

2020 ◽  
Author(s):  
Adriana Savova ◽  
Julia Romanov ◽  
Sascha Martens
Keyword(s):  
Phase Separation ◽  
Wild Type ◽  
Selective Autophagy ◽  
Ubiquitinated Proteins ◽  
Cargo Receptor ◽  
Condensate Formation ◽  
Uba Domain ◽  
Reconstituted System ◽  
Pb1 Domain

SummarySelective autophagy removes harmful intracellular structures such as ubiquitinated, aggregated proteins ensuring cellular homeostasis. This is achieved by the encapsulation of this cargo material within autophagosomes. The cargo receptor p62/SQSTM1 mediates the phase separation of ubiquitinated proteins into condensates, which subsequently become targets for the autophagy machinery. NBR1, another cargo receptor, is a crucial regulator of condensate formation. The mechanisms of the interplay between p62 and NBR1 are not well understood. Employing a fully reconstituted system we show that two domains of NBR1, the PB1 domain which binds to p62 and the UBA domain which binds to ubiquitin, are required to promote p62-ubiquitin condensate formation. In cells, acute depletion of endogenous NBR1 reduces formation of p62 condensates, a phenotype that can be rescued by re-expression of wild-type NBR1, but not PB1 or UBA domain mutants. Our results provide mechanistic insights into the role of NBR1 in selective autophagy.

scholarly journals Overexpression of the Selective Autophagy Cargo Receptor NBR1 Modifies Plant Response to Sulfur Deficit

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 669 ◽  
Author(s):  
Leszek Tarnowski ◽  
Milagros Collados Rodriguez ◽  
Jerzy Brzywczy ◽  
Dominik Cysewski ◽  
Anna Wawrzynska ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Kinase Inhibitors ◽  
Biological Significance ◽  
Direct Interaction ◽  
Ribosomal Gene ◽  
Plant Response ◽  
Wild Type ◽  
Selective Autophagy ◽  
Cargo Receptor

Plants exposed to sulfur deficit elevate the transcription of NBR1 what might reflect an increased demand for NBR1 in such conditions. Therefore, we investigated the role of this selective autophagy cargo receptor in plant response to sulfur deficit (-S). Transcriptome analysis of the wild type and NBR1 overexpressing plants pointed out differences in gene expression in response to -S. Our attention focused particularly on the genes upregulated by -S in roots of both lines because of significant overrepresentation of cytoplasmic ribosomal gene family. Moreover, we noticed overrepresentation of the same family in the set of proteins co-purifying with NBR1 in -S. One of these ribosomal proteins, RPS6 was chosen for verification of its direct interaction with NBR1 and proven to bind outside the NBR1 ubiquitin binding domains. The biological significance of this novel interaction and the postulated role of NBR1 in ribosomes remodeling in response to starvation remain to be further investigated. Interestingly, NBR1 overexpressing seedlings have significantly shorter roots than wild type when grown in nutrient deficient conditions in the presence of TOR kinase inhibitors. This phenotype probably results from excessive autophagy induction by the additive effect of NBR1 overexpression, starvation, and TOR inhibition.

scholarly journals The Autophagy Cargo Receptor SQSTM1 Inhibits Infectious Bursal Disease Virus Infection through Selective Autophagic Degradation of Double-Stranded Viral RNA

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2494
Author(s):  
Chenyang Xu ◽  
Tongtong Li ◽  
Jing Lei ◽  
Yina Zhang ◽  
Jiyong Zhou ◽  
...  
Keyword(s):  
Disease Virus ◽  
Infectious Bursal Disease Virus ◽  
Acid Sites ◽  
Infectious Bursal Disease ◽  
Structured Illumination Microscopy ◽  
Viral Dsrna ◽  
Selective Autophagy ◽  
Cargo Receptor ◽  
Bursal Disease

Selective autophagy mediates the degradation of cytoplasmic cargos, such as damaged organelles, invading pathogens, and protein aggregates. However, whether it targets double-stranded RNA (dsRNA) of intracellular pathogens is still largely unknown. Here, we show that selective autophagy regulates the degradation of the infectious bursal disease virus (IBDV) dsRNA genome. The amount of dsRNA decreased greatly in cells that overexpressed the autophagy-required protein VPS34 or autophagy cargo receptor SQSTM1, while it increased significantly in SQSTM1 or VPS34 knockout cells or by treating wild-type cells with the autophagy inhibitor chloroquine or wortmannin. Confocal microscopy and structured illumination microscopy showed SQSTM1 colocalized with dsRNA during IBDV infection. A pull-down assay further confirmed the direct binding of SQSTM1 to dsRNA through amino acid sites R139 and K141. Overexpression of SQSTM1 inhibited the replication of IBDV, while knockout of SQSTM1 promoted IBDV replication. Therefore, our findings reveal the role of SQSTM1 in clearing viral dsRNA through selective autophagy, highlighting the antiviral role of autophagy in the removal of the viral genome.

scholarly journals Non-autophagy role of Atg5 and NBR1 in unconventional secretion of IL-12 prevents gut dysbiosis and inflammation

2020 ◽  
Author(s):  
Seth D. Merkley ◽  
Samuel M. Goodfellow ◽  
Yan Guo ◽  
Zoe E.R. Wilton ◽  
Janie R. Byrum ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Myeloid Cells ◽  
Late Endosome ◽  
Gut Dysbiosis ◽  
Cargo Receptor ◽  
Unconventional Secretion ◽  
Genetic Deletion

ABSTRACTIntestinal myeloid cells play a critical role in balancing intestinal homeostasis and inflammation. Here, we report that expression of the autophagy related 5 (Atg5) protein in myeloid cells prevents dysbiosis and excessive intestinal inflammation by limiting IL-12 production. Mice with a selective genetic deletion of Atg5 in myeloid cells (Atg5ΔMye) showed signs of dysbiosis prior to colitis and exhibited severe intestinal inflammation upon colitis induction that was characterized by increased IFNγ production. This increase in IFNγ was due to excess IL-12 secretion from Atg5-deficient myeloid cells. Atg5 functions to limit IL-12 secretion through modulation of late endosome (LE) acidity. Additionally, the autophagy cargo receptor NBR1, which accumulates in Atg5-deficient cells, played a role by delivering IL-12 to LE. Restoration of the intestinal microbiota and alleviation of intestinal inflammation was achieved by genetic deletion of IL-12 in Atg5ΔMye mice. In summary, Atg5 expression in intestinal myeloid cells acts as an anti-inflammatory brake to regulate IL-12 thus preventing dysbiosis and uncontrolled IFNγ-driven intestinal inflammation.

scholarly journals Deregulation of selective autophagy during aging and pulmonary fibrosis: the role of TGF β1

Aging Cell ◽  
2015 ◽  
Vol 14 (5) ◽  
pp. 774-783 ◽  
Author(s):  
Meredith L. Sosulski ◽  
Rafael Gongora ◽  
Svitlana Danchuk ◽  
Chunmin Dong ◽  
Fayong Luo ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Selective Autophagy ◽  
Tgf Β1

Mitochondrial Quality Control and Restraining Innate Immunity

2020 ◽  
Vol 36 (1) ◽  
pp. 265-289
Author(s):  
Andrew T. Moehlman ◽  
Richard J. Youle
Keyword(s):  
Innate Immunity ◽  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Interferon Response ◽  
Mitochondrial Quality Control ◽  
Selective Autophagy ◽  
Eukaryotic Organisms ◽  
And Function

Maintaining mitochondrial health is essential for the survival and function of eukaryotic organisms. Misfunctioning mitochondria activate stress-responsive pathways to restore mitochondrial network homeostasis, remove damaged or toxic proteins, and eliminate damaged organelles via selective autophagy of mitochondria, a process termed mitophagy. Failure of these quality control pathways is implicated in the pathogenesis of Parkinson's disease and other neurodegenerative diseases. Impairment of mitochondrial quality control has been demonstrated to activate innate immune pathways, including inflammasome-mediated signaling and the antiviral cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)–regulated interferon response. Immune system malfunction is a common hallmark in many neurodegenerative diseases; however, whether inflammation suppresses or exacerbates disease pathology is still unclear. The goal of this review is to provide a historical overview of the field, describe mechanisms of mitochondrial quality control, and highlight recent advances on the emerging role of mitochondria in innate immunity and inflammation.

scholarly journals Hrr25 triggers selective autophagy–related pathways by phosphorylating receptor proteins

2014 ◽  
Vol 207 (1) ◽  
pp. 91-105 ◽  
Author(s):  
Chikara Tanaka ◽  
Li-Jing Tan ◽  
Keisuke Mochida ◽  
Hiromi Kirisako ◽  
Michiko Koizumi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Basis ◽  
Receptor Proteins ◽  
Selective Autophagy ◽  
The Core ◽  
The Common ◽  
Related Proteins

In selective autophagy, degradation targets are specifically recognized, sequestered by the autophagosome, and transported into the lysosome or vacuole. Previous studies delineated the molecular basis by which the autophagy machinery recognizes those targets, but the regulation of this process is still poorly understood. In this paper, we find that the highly conserved multifunctional kinase Hrr25 regulates two distinct selective autophagy–related pathways in Saccharomyces cerevisiae. Hrr25 is responsible for the phosphorylation of two receptor proteins: Atg19, which recognizes the assembly of vacuolar enzymes in the cytoplasm-to-vacuole targeting pathway, and Atg36, which recognizes superfluous peroxisomes in pexophagy. Hrr25-mediated phosphorylation enhances the interactions of these receptors with the common adaptor Atg11, which recruits the core autophagy-related proteins that mediate the formation of the autophagosomal membrane. Thus, this study introduces regulation of selective autophagy as a new role of Hrr25 and, together with other recent studies, reveals that different selective autophagy–related pathways are regulated by a uniform mechanism: phosphoregulation of the receptor–adaptor interaction.

scholarly journals Role of Selective Autophagy in Spermatogenesis and Male Fertility

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2523
Author(s):  
Chunyu Lv ◽  
Xiaoli Wang ◽  
Ying Guo ◽  
Shuiqiao Yuan
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Genetic Regulation ◽  
Underlying Mechanism ◽  
Intracellular Pathogens ◽  
Selective Autophagy ◽  
Reproductive Processes ◽  
Infertile Patients ◽  
Shed Light

Autophagy is a “self-eating” process that engulfs cellular contents for their subsequent digestion in lysosomes to engage the metabolic need in response to starvation or environmental insults. According to the contents of degradation, autophagy can be divided into bulk autophagy (non-selective autophagy) and selective autophagy. Bulk autophagy degrades non-specific cytoplasmic materials in response to nutrient starvation while selective autophagy targets specific cargoes, such as damaged organelles, protein aggregates, and intracellular pathogens. Selective autophagy has been documented to relate to the reproductive processes, especially for the spermatogenesis, fertilization, and biosynthesis of testosterone. Although selective autophagy is vital in the field of reproduction, its role and the underlying mechanism have remained unclear. In this review, we focus on selective autophagy to discuss the recent advances in our understanding of the mechanism and role of selective autophagy on spermatogenesis and male fertility in mammals. Understanding the role of selective autophagy during spermatogenesis will promote the recognition of genetic regulation in male infertility, and shed light on therapies of infertile patients.

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