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https://www.readbyqxmd.com/read/28822762/rab11a-is-required-for-porcine-reproductive-and-respiratory-syndrome-virus-induced-autophagy-to-promote-viral-replication
#1
Kai Wang, Shuaifeng Li, Tesfaye Worku, Xingjie Hao, Liaohan Yang, Shujun Zhang
Porcine reproductive and respiratory syndrome virus (PRRSV) is the leading virus known to cause massive economic loss in pig industry worldwide. In our previous study, transcriptional profiling of PRRSV-infected lung tissue of Tongcheng and landrane pigs, which have highly pathogenic PRRSV (HP-PRRSV) susceptibility differences, showed differential expression of Rab11a. The small GTPase Rab11a regulates intracellular membrane trafficking events involved in autophagy. However, the involvement of convergence of endosomal Rab11a and autophagy pathways during PRRSV infection is still unclear...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28821724/atg4-proteolytic-activity-can-be-inhibited-by-atg1-phosphorylation
#2
Jana Sánchez-Wandelmer, Franziska Kriegenburg, Sabrina Rohringer, Martina Schuschnig, Rubén Gómez-Sánchez, Bettina Zens, Susana Abreu, Ralph Hardenberg, David Hollenstein, Jieqiong Gao, Christian Ungermann, Sascha Martens, Claudine Kraft, Fulvio Reggiori
The biogenesis of autophagosomes depends on the conjugation of Atg8-like proteins with phosphatidylethanolamine. Atg8 processing by the cysteine protease Atg4 is required for its covalent linkage to phosphatidylethanolamine, but it is also necessary for Atg8 deconjugation from this lipid to release it from membranes. How these two cleavage steps are coordinated is unknown. Here we show that phosphorylation by Atg1 inhibits Atg4 function, an event that appears to exclusively occur at the site of autophagosome biogenesis...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28821708/a-reversible-phospho-switch-mediated-by-ulk1-regulates-the-activity-of-autophagy-protease-atg4b
#3
N Pengo, A Agrotis, K Prak, J Jones, R Ketteler
Upon induction of autophagy, the ubiquitin-like protein LC3 is conjugated to phosphatidylethanolamine (PE) on the inner and outer membrane of autophagosomes to allow cargo selection and autophagosome formation. LC3 undergoes two processing steps, the proteolytic cleavage of pro-LC3 and the de-lipidation of LC3-PE from autophagosomes, both executed by the same cysteine protease ATG4. How ATG4 activity is regulated to co-ordinate these events is currently unknown. Here we find that ULK1, a protein kinase activated at the autophagosome formation site, phosphorylates human ATG4B on serine 316...
August 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28821398/urate-promotes-snca-%C3%AE-synuclein-clearance-via-regulating-mtor-dependent-macroautophagy
#4
Yu-Lan Sheng, Xing Chen, Xiao-Ou Hou, Xin-Yuan, Bao-Shi Yuan, Yu-Qing Yuan, Qi-Lin Zhang, Xian Cao, Chun-Feng Liu, Wei-Feng Luo, Li-Fang Hu
Serum urate levels are reported to be significantly lowered in patients with Parkinson's disease (PD) and inversely correlated to the risk and progression of PD. However, the mechanism by which urate affects PD is poorly understood. Here we showed that treatment with uric acid (UA) resulted in an autophagy activity enhancement in PC12 cells in dose- and time-dependent manners, as indicated by LC3-II increase and P62 decrease. Moreover, UA was still able to increase the LC3-II level and the number of LC3 puncta in the presence of Bafilomycin A1, a lysosomal inhibitor...
August 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28820312/architecture-of-the-atg2b-wdr45-complex-and-an-aromatic-y-hf-motif-crucial-for-complex-formation
#5
Jing-Xiang Zheng, Yan Li, Yue-He Ding, Jun-Jie Liu, Mei-Jun Zhang, Meng-Qiu Dong, Hong-Wei Wang, Li Yu
PtdIns3P signaling is critical for dynamic membrane remodeling during autophagosome formation. Proteins in the Atg18/WIPI family are PtdIns3P-binding effectors which can form complexes with proteins in the Atg2 family, and both families are essential for macroautophagy/autophagy. However, little is known about the biophysical properties and biological functions of the Atg2-Atg18/WIPI complex as a whole. Here, we demonstrate that an ortholog of yeast Atg18, mammalian WDR45/WIPI4 has a stronger binding capacity for mammalian ATG2A or ATG2B than the other 3 WIPIs...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820297/the-formation-of-autophagosomes-during-lysosomal-defect-a-new-source-of-cytotoxicity
#6
Robert W Button, Shouqing Luo
Macroautophagy/autophagy comprises autophagosome synthesis and lysosomal degradation. It is well known that lysosomal defects cause toxicity to cells. However, it has not been investigated previously if cytotoxicity is conferred by autophagosome formation during lysosomal defect. Recently, we found that the formation of autophagosomes in such conditions also causes cytotoxicity, in addition to lysosomal defect insults. We revealed that a partial reduction in autophagosome synthesis was beneficial for cell survival in cells bearing the autophagosome formation-based toxicity...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28820282/mir505-3p-regulates-axonal-development-via-inhibiting-the-autophagy-pathway-by-targeting-atg12
#7
Kan Yang, Bin Yu, Cheng Cheng, Tianlin Cheng, Bo Yuan, Kai Li, Junhua Xiao, Zilong Qiu, Yuxun Zhou
In addition to the canonical role in protein homeostasis, autophagy has recently been found to be involved in axonal dystrophy and neurodegeneration. Whether autophagy may also be involved in neural development remains largely unclear. Here we report that Mir505-3p is a crucial regulator for axonal elongation and branching in vitro and in vivo, through modulating autophagy in neurons. We identify that the key target gene of Mir505-3p in neurons is Atg12, encoding ATG12 (autophagy related 12) which is an essential component of the autophagy machinery during the initiation and expansion steps of autophagosome formation...
August 18, 2017: Autophagy
https://www.readbyqxmd.com/read/28819237/disruption-of-the-plant-specific-cfs1-gene-impairs-autophagosome-turnover-and-triggers-eds1-dependent-cell-death
#8
Arpaporn Sutipatanasomboon, Stefanie Herberth, Ellen G Alwood, Heidrun Häweker, Britta Müller, Mojgan Shahriari, Anke Y Zienert, Birger Marin, Silke Robatzek, Gerrit J K Praefcke, Kathryn R Ayscough, Martin Hülskamp, Swen Schellmann
Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819214/hiv-1-nef-induced-cardiotoxicity-through-dysregulation-of-autophagy
#9
Manish K Gupta, Rafal Kaminski, Brian Mullen, Jennifer Gordon, Tricia H Burdo, Joseph Y Cheung, Arthur M Feldman, Muniswamy Madesh, Kamel Khalili
Cardiovascular disease is a leading cause of co-morbidity in HIV-1 positive patients, even those in whom plasma virus levels are well-controlled. The pathogenic mechanism of HIV-1-associated cardiomyopathy is unknown, but has been presumed to be mediated indirectly, owing to the absence of productive HIV-1 replication in cardiomyocytes. We sought to investigate the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4+ T cells on protein quality control and autophagy in cardiomyocytes...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819100/blockage-of-the-lysosome-dependent-autophagic-pathway-contributes-to-complement-membrane-attack-complex-induced-podocyte-injury-in-idiopathic-membranous-nephropathy
#10
Wei Jing Liu, Zhi-Hang Li, Xiao-Cui Chen, Xiao-Lu Zhao, Zhen Zhong, Chen Yang, Hong-Luan Wu, Ning An, Wei-Yan Li, Hua-Feng Liu
Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model. The lysosomal turnover of LC3-II was not influenced, although the BECN1 expression level was upregulated after exposure of podocytes to C5b-9...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28816597/the-ulk-complex-initiates-autophagosome-formation-at-phosphatidylinositol-synthase-enriched-er-subdomains
#11
Taki Nishimura, Noboru Mizushima
In our recent paper, we biochemically analyzed autophagosome-related membranes at the initiation stage of macroautophagy/autophagy using atg knockout (KO) cells and demonstrated that the ULK complex is recruited to 2 distinct membranes: the ER membrane and ATG9A-positive autophagosome precursors. We have also identified phosphatidylinositol synthase (PIS)-enriched ER subdomains as the initiation site of autophagosome formation. Based on these findings, we propose that the ULK complex, the PIS-enriched ER subdomain, and ATG9A vesicles together initiate autophagosome formation...
August 17, 2017: Autophagy
https://www.readbyqxmd.com/read/28816419/tubulin-acetylation-accompanies-autophagy-development-induced-by-different-abiotic-stimuli-in-arabidopsis-thaliana
#12
Vira Olenieva, Dmytro Lytvyn, Alla Yemets, Catherine Bergounioux, Yaroslav Blume
Microtubules (MTs) play an important role in the regulation of autophagy development in yeast and animal as well as in plant cells. MTs participate in maturation and traffic of autophagosomes through their dynamic state changes and post-translational modifications of tubulin, namely acetylation. We subjected Arabidopsis thaliana seedlings to metabolic-, salt-, osmotic stresses as well as irradiation of ultraviolet B and investigated the involvement of plant MTs in the development of stress-induced autophagy via tubulin acetylation...
August 17, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28816044/action-of-gold-nanospikes-based-nanoradiosensitizers-cellular-internalization-radiotherapy-and-autophagy
#13
Ningning Ma, Peidang Liu, Nongyue He, Ning Gu, Fu-Gen Wu, Zhan Chen
A major challenge to achieve effective X-ray radiation therapy is to use a relatively low and safe radiation dose. Various radiosensitizers, which can significantly enhance the radiotherapeutic performance, have been developed. Gold-based nanomaterials, as a new type of nanoparticle-based radiosensitizers, have been extensively used in researches involving cancer radiotherapy. However, the cancer therapeutic effect using the gold nanoparticle-based radiotherapy is usually not significant because of the low cellular uptake efficiency and the autophagy-inducing ability of these gold nanomaterials...
August 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28815487/benzophenone-3-impairs-autophagy-alters-epigenetic-status-and-disrupts-retinoid-x-receptor-signaling-in-apoptotic-neuronal-cells
#14
Agnieszka Wnuk, Joanna Rzemieniec, Władysław Lasoń, Wojciech Krzeptowski, Małgorzata Kajta
Benzophenone-3 (BP-3) is the most widely used compound among UV filters for the prevention of photodegradation. Population studies have demonstrated that it penetrates through the skin and crosses the blood-brain barrier. However, little is known about the impact of BP-3 on the nervous system and its possible adverse effects on the developing brain. We demonstrated that the neurotoxic effects of BP-3 were accompanied by the induction of apoptosis, as evidenced by apoptosis-related caspase-3 activation and apoptotic body formation as well as the inhibition of autophagy, as determined by the downregulation of autophagy-related genes, decreased autophagosome formation, and reduced LC3B-to-LC3A ratio...
August 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28815060/defective-expression-of-atg4d-abrogates-autophagy-and-promotes-growth-in-human-uterine-fibroids
#15
Abdeljabar El Andaloussi, Samar Habib, Gizem Soylemes, Archana Laknaur, Heba Elhusseini, Ayman Al-Hendy, Nahed Ismail
Uterine fibroids (UF) are the most common pelvic tumors in women of reproductive-age and they usually cause heavy menstrual bleeding, pain and infertility. Autophagy is a collection of processes that enables the cells to digest and recycle their cytoplasmic contents, such as toxic protein aggregates, defunct or disused organelles and invading microorganisms. Dysregulation in autophagy process were described in neoplasms; however, the contribution of autophagy to the pathogenesis of UF remains unknown. In this study, we demonstrate that autophagy is deregulated in human UF as evidenced by significant accumulation of autophagosome in human UF cells compared to normal myometrium cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28813441/cross-over-endocytosis-of-claudins-is-mediated-by-interactions-via-their-extracellular-loops
#16
Nora Gehne, Agathe Lamik, Martin Lehmann, Reiner F Haseloff, Anuska V Andjelkovic, Ingolf E Blasig
Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, the mechanisms allowing TJ remodeling while maintaining barrier integrity are largely unknown. Cldns and occludin are heterophilically and homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed the presence of Cldns in these vesicles and revealed a distinct separation of Cldns derived from opposing cells within cross-over endocytosed vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/28813193/local-detection-of-ptdins3p-at-autophagosome-biogenesis-membrane-platforms
#17
Anna Chiara Nascimbeni, Patrice Codogno, Etienne Morel
Phosphatidylinositol 3-phosphate (PtdIns3P) is a key player of membrane trafficking regulation, mostly synthesized by the PIK3C3 lipid kinase. The presence of PtdIns3P on endosomes has been demonstrated; however, the role and dynamics of the pool of PtdIns3P dedicated to macroautophagy/autophagy remains elusive. Here we addressed this question by studying the mobilization of PtdIns3P in time and space during autophagosome biogenesis. We compared different dyes known to specifically detect PtdIns3P by fluorescence microscopy analysis, based on PtdIns3P-binding FYVE and PX domains, and show that these transfected dyes induce defects in endosomal dynamics as well as artificial and sustained autophagosome formation...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28813181/pathway-choice-between-proteasomal-and-autophagic-degradation
#18
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Efficient degradation of abnormal or aggregated proteins is crucial to protect the cell against proteotoxic stress. Selective targeting and disposal of such proteins usually occurs in a ubiquitin-dependent manner by proteasomes and macroautophagy/autophagy. Whereas proteasomes are efficient in degrading abnormal soluble proteins, protein aggregates are typically targeted for degradation by autophagic vesicles. Both processes require ubiquitin-binding receptors, which are targeted to proteasomes via ubiquitin-like domains or to phagophores (the precursors to autophagosomes) via Atg8/LC3 binding motifs, respectively...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28812433/regulation-of-sqstm1-p62-via-uba-domain-ubiquitination-and-its-role-in-disease
#19
YouJin Lee, Conrad C Weihl
Macroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28808307/lc3a-silencing-hinders-aggresome-vimentin-cage-clearance-in-primary-choroid-plexus-carcinoma
#20
Marwa Nassar, Heba Samaha, Myret Ghabriel, Maha Yehia, Hala Taha, Sherin Salem, Khaled Shaaban, Mariam Omar, Nabil Ahmed, Shahenda El-Naggar
Aggresomes are transient microtubule-dependent inclusion bodies that sequester misfolded proteins and are ultimately removed by autophagy. Here we report the generation of a choroid plexus carcinoma cell line; Children's Cancer Hospital Egypt (CCHE)-45, which is characterized by the constitutive formation of aggresomes. When examining the autophagy pathway as the main route for aggresomes clearance, CCHE-45 cells displayed increased autophagy flux mediated by MAP1LC3B. MAP1LC3A-Variant1 gene expression was silenced by promoter methylation...
August 14, 2017: Scientific Reports
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