keyword
https://read.qxmd.com/read/38536036/the-gtpase-activating-protein-gyp7-regulates-rab7-ypt7-activity-on-late-endosomes
#1
JOURNAL ARTICLE
Nadia Füllbrunn, Raffaele Nicastro, Muriel Mari, Janice Griffith, Eric Herrmann, René Rasche, Ann-Christin Borchers, Kathrin Auffarth, Daniel Kümmel, Fulvio Reggiori, Claudio De Virgilio, Lars Langemeyer, Christian Ungermann
Organelles of the endomembrane system contain Rab GTPases as identity markers. Their localization is determined by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). It remains largely unclear how these regulators are specifically targeted to organelles and how their activity is regulated. Here, we focus on the GAP Gyp7, which acts on the Rab7-like Ypt7 protein in yeast, and surprisingly observe the protein exclusively in puncta proximal to the vacuole. Mistargeting of Gyp7 to the vacuole strongly affects vacuole morphology, suggesting that endosomal localization is needed for function...
June 3, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38489378/alix-and-tsg101-are-essential-for-cellular-entry-and-replication-of-two-porcine-alphacoronaviruses
#2
JOURNAL ARTICLE
Xiongnan Chen, Yifan Liang, Zhijun Weng, Chen Hu, Yunzhao Peng, Yingshuo Sun, Qi Gao, Zhao Huang, Shengqiu Tang, Lang Gong, Guihong Zhang
Alphacoronaviruses are the primary coronaviruses responsible for causing severe economic losses in the pig industry with the potential to cause human outbreaks. Currently, extensive studies have reported the essential role of endosomal sorting and transport complexes (ESCRT) in the life cycle of enveloped viruses. However, very little information is available about which ESCRT components are crucial for alphacoronaviruses infection. By using RNA interference in combination with Co-immunoprecipitation, as well as fluorescence and electron microscopy approaches, we have dissected the role of ALIX and TSG101 for two porcine alphacoronavirus cellular entry and replication...
March 15, 2024: PLoS Pathogens
https://read.qxmd.com/read/38483999/distinct-early-role-of-pten-regulation-during-hcmv-infection-of-monocytes
#3
JOURNAL ARTICLE
Liudmila S Chesnokova, Bailey S Mosher, Heather L Fulkerson, Hyung W Nam, Akhalesh K Shakya, Andrew D Yurochko
Human cytomegalovirus (HCMV) infection of monocytes is essential for viral dissemination and persistence. We previously identified that HCMV entry/internalization and subsequent productive infection of this clinically relevant cell type is distinct when compared to other infected cells. We showed that internalization and productive infection required activation of epidermal growth factor receptor (EGFR) and integrin/c-Src, via binding of viral glycoprotein B to EGFR, and the pentamer complex to β1/β3 integrins...
March 19, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38467968/mitochondrial-damage-and-clearance-in-retinal-pigment-epithelial-cells
#4
JOURNAL ARTICLE
Iswariyaraja Sridevi Gurubaran
Age-related macular degeneration (AMD) is a devastating eye disease that causes permanent vision loss in the central part of the retina, known as the macula. Patients with such severe visual loss face a reduced quality of life and are at a 1.5 times greater risk of death compared to the general population. Currently, there is no cure for or effective treatment for dry AMD. There are several mechanisms thought to underlie the disease, for example, ageing-associated chronic oxidative stress, mitochondrial damage, harmful protein aggregation and inflammation...
March 2024: Acta Ophthalmologica
https://read.qxmd.com/read/38448982/defects-of-mitochondria-lysosomes-communication-induce-secretion-of-mitochondria-derived-vesicles-and-drive-chemoresistance-in-ovarian-cancer-cells
#5
JOURNAL ARTICLE
Sinforosa Gagliardi, Marco Mitruccio, Riccardo Di Corato, Roberta Romano, Alessandra Aloisi, Rosaria Rinaldi, Pietro Alifano, Flora Guerra, Cecilia Bucci
BACKGROUND: Among the mechanisms of mitochondrial quality control (MQC), generation of mitochondria-derived vesicles (MDVs) is a process to avoid complete failure of mitochondria determining lysosomal degradation of mitochondrial damaged proteins. In this context, RAB7, a late endocytic small GTPase, controls delivery of MDVs to late endosomes for subsequent lysosomal degradation. We previously demonstrated that RAB7 has a pivotal role in response to cisplatin (CDDP) regulating resistance to the drug by extracellular vesicle (EVs) secretion...
March 6, 2024: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/38448435/sars-cov-2-virulence-factor-orf3a-blocks-lysosome-function-by-modulating-tbc1d5-dependent-rab7-gtpase-cycle
#6
JOURNAL ARTICLE
Kshitiz Walia, Abhishek Sharma, Sankalita Paul, Priya Chouhan, Gaurav Kumar, Rajesh Ringe, Mahak Sharma, Amit Tuli
SARS-CoV-2, the causative agent of COVID-19, uses the host endolysosomal system for entry, replication, and egress. Previous studies have shown that the SARS-CoV-2 virulence factor ORF3a interacts with the lysosomal tethering factor HOPS complex and blocks HOPS-mediated late endosome and autophagosome fusion with lysosomes. Here, we report that SARS-CoV-2 infection leads to hyperactivation of the late endosomal and lysosomal small GTP-binding protein Rab7, which is dependent on ORF3a expression. We also observed Rab7 hyperactivation in naturally occurring ORF3a variants encoded by distinct SARS-CoV-2 variants...
March 6, 2024: Nature Communications
https://read.qxmd.com/read/38445453/sirt1-rab7-axis-attenuates-nlrp3-and-sting-activation-through-late-endosomal-dependent-mitophagy-during-sepsis-induced-acute-lung-injury
#7
JOURNAL ARTICLE
Tao Jiang, Enran Liu, Zhiyuan Li, Congmin Yan, Xiaoyun Zhang, Jingting Guan, Yuanbo Zhan, Bo Zhao, Wengang Ding
BACKGROUND: Acute lung injury (ALI) is a leading cause of mortality in patients with sepsis due to proinflammatory endothelial changes and endothelial permeability defects. Mitochondrial dysfunction is recognized as a critical mediator in the pathogenesis of sepsis-induced ALI. Although mitophagy regulation of mitochondrial quality is well recognized, little is known about its role in lung ECs during sepsis-induced ALI. Sirtuin 1 (SIRT1) is a histone protein deacetylase involved in inflammation, mitophagy, and cellular senescence...
March 4, 2024: International Journal of Surgery
https://read.qxmd.com/read/38444141/-research-progress-on-the-role-of-tank-binding-kinase-1-in-pink1-parkin-dependent-and-independent-mitophagy
#8
JOURNAL ARTICLE
Hao Deng, Zhi Xia, Hua-Yu Shang
Mitophagy is a process that selectively removes excess or damaged mitochondria and plays an important role in regulating intracellular mitochondrial mass and maintaining mitochondrial energy metabolism. TANK-binding kinase 1 (TBK1) is a multifunctional serine/threonine protein kinase, which is involved in the regulation of PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent and -independent mitophagy. Recent studies have shown that TBK1 phosphorylates the autophagy related proteins, such as optineurin (OPTN), p62/sequestosome-1, Ras-related GTP binding protein 7 (Rab7), and mediates the binding of nuclear dot protein 52 (NDP52) to UNC-51 like autophagy activating kinase 1 (ULK1) complex, as well as the binding of TAX1-binding protein 1 (TAX1BP1) to microtubule-associated protein 1 light chain 3 (LC3), thereby enhancing PINK1/Parkin-dependent mitophagy...
February 25, 2024: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://read.qxmd.com/read/38427241/internalization-and-endosomal-trafficking-of-extracellular-tau-in-microglia-improved-by-%C3%AE-linolenic-acid
#9
JOURNAL ARTICLE
Smita Eknath Desale, Hariharakrishnan Chidambaram, Tazeen Qureshi, Subashchandrabose Chinnathambi
Alzheimer's disease (AD) is distinguished by extracellular accumulation of amyloid-beta plaques and intracellular neurofibrillary tangles of Tau. Pathogenic Tau species are also known to display "prion-like propagation," which explains their presence in extracellular spaces as well. Glial population, especially microglia, tend to proclaim neuroinflammatory condition, disrupted signaling mechanisms, and cytoskeleton deregulation in AD. Omega-3 fatty acids play a neuroprotective role in the brain, which can trigger the anti-inflammatory pathways as well as actin dynamics in the cells...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38422876/the-size-dependence-and-reversibility-of-polystyrene-nanoplastics-induced-lipid-accumulation-in-mice-possible-roles-of-lysosomes
#10
JOURNAL ARTICLE
Yan-Yang Lu, Lu Lu, Hong-Yun Ren, Weizhen Hua, Nengxing Zheng, Fu-Yi Huang, Jiani Wang, Meiping Tian, Qingyu Huang
Nanoplastics (NPs) continue to accumulate in global aquatic and terrestrial systems, posing a potential threat to human health through the food chain and/or other pathways. Both in vivo and in vitro studies have confirmed that the liver is one of the main organs targeted for the accumulation of NPs in living organisms. However, whether exposure to NPs induces size-dependent disorders of liver lipid metabolism remains controversial, and the reversibility of NPs-induced hepatotoxicity is largely unknown. In this study, the effects of long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs) on lipid accumulation were investigated in terms of autophagy and lysosomal mechanisms...
February 24, 2024: Environment International
https://read.qxmd.com/read/38401056/intraluminal-vesicle-trafficking-is-involved-in-the-secretion-of-base-excision-repair-protein-ape1
#11
JOURNAL ARTICLE
Isabella Parolini, Monica Degrassi, Francesca Spadaro, Federica Caponnetto, Katia Fecchi, Serena Mastantuono, Xue Zhouyiyuan, Bruce Demple, Daniela Cesselli, Gianluca Tell
The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is an essential enzyme of the base excision repair pathway of non-distorting DNA lesions. In response to genotoxic treatments, APE1 is highly secreted (sAPE1) in association with small-extracellular vesicles (EVs). Interestingly, its presence in the serum of patients with hepatocellular or non-small-cell-lung cancers may represent a prognostic biomarker. The mechanism driving APE1 to associate with EVs is unknown, but is of paramount importance in better understanding the biological roles of sAPE1...
February 24, 2024: FEBS Journal
https://read.qxmd.com/read/38344192/molecular-structures-and-function-of-the-autophagosome-lysosome-fusion-machinery
#12
JOURNAL ARTICLE
Jiajie Diao, Calvin K Yip, Qing Zhong
Macroautophagy (also known as autophagy) plays a pivotal role in maintaining cellular homeostasis. The terminal step of the multi-step autophagy degradation pathway involves fusion between the cargo-laden, double-membraned autophagosome and the lytic organelle lysosome/vacuole. Over the past decade, various core components of the molecular machinery that execute this critical terminal autophagy event have been identified. This review highlights recent advances in understanding the molecular structures, biochemical functions, and regulatory mechanisms of key components of this highly sophisticated machinery including the SNARE fusogens, tethering factors, Rab GTPases and associated guanine nucleotide exchange factors, and other accessory factors...
2024: Autophagy Rep
https://read.qxmd.com/read/38319117/phylogenomic-structural-and-cell-biological-analyses-reveal-that-stenotrophomonas-maltophilia-replicates-in-acidified-rab7a-positive-vacuoles-of-acanthamoeba-castellanii
#13
JOURNAL ARTICLE
Javier Rivera, Julio C Valerdi-Negreros, Diana M Vázquez-Enciso, Fulvia-Stefany Argueta-Zepeda, Pablo Vinuesa
Acanthamoeba species are clinically relevant free-living amoebae (FLA) ubiquitously found in soil and water bodies. Metabolically active trophozoites graze on diverse microbes via phagocytosis. However, functional studies on Rab GTPases (Rabs), which are critical for controlling vesicle trafficking and maturation, are scarce for this FLA. This knowledge gap can be partly explained by the limited genetic tools available for Acanthamoeba cell biology. Here, we developed plasmids to generate fusions of A. castellanii strain Neff proteins to the N- or C-termini of mEGFP and mCherry2...
February 6, 2024: Microbiology Spectrum
https://read.qxmd.com/read/38315726/endolysosomal-trafficking-controls-yolk-granule-biogenesis-in-vitellogenic-drosophila-oocytes
#14
JOURNAL ARTICLE
Yue Yu, Dongsheng Chen, Stephen M Farmer, Shiyu Xu, Beatriz Rios, Amanda Solbach, Xin Ye, Lili Ye, Sheng Zhang
Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development...
February 5, 2024: PLoS Genetics
https://read.qxmd.com/read/38296463/role-of-the-cytosolic-domain-of-the-a3-subunit-of-v-atpase-in-the-interaction-with-rab7-and-secretory-lysosome-trafficking-in-osteoclasts
#15
JOURNAL ARTICLE
Mayumi Nakanishi-Matsui, Naomi Matsumoto, Ge-Hong Sun-Wada, Yoh Wada
We previously reported that the a3 subunit of proton-pumping vacuolar-type ATPase (V-ATPase) interacts with Rab7 and its guanine nucleotide exchange factor, Mon1a-Ccz1, and recruits them to secretory lysosomes in osteoclasts, which is essential for anterograde trafficking of secretory lysosomes. The a3 subunit interacts with Mon1a-Ccz1 through its cytosolic N-terminal domain. Here, we examined the roles of this domain in the interaction with Rab7 and trafficking of secretory lysosomes. Immunoprecipitation experiments showed that a3 interacted with Rab7 through its cytosolic domain, similar to the interaction with Mon1a-Ccz1...
2024: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/38277448/ku70-senses-cytosolic-dna-and-assembles-a-tumor-suppressive-signalosome
#16
JOURNAL ARTICLE
Abhimanu Pandey, Cheng Shen, Shouya Feng, Daniel Enosi Tuipulotu, Chinh Ngo, Cheng Liu, Melan Kurera, Anukriti Mathur, Shweta Venkataraman, Jing Zhang, Dipti Talaulikar, Renhua Song, Justin J-L Wong, Narci Teoh, Nadeem O Kaakoush, Si Ming Man
The innate immune response contributes to the development or attenuation of acute and chronic diseases, including cancer. Microbial DNA and mislocalized DNA from damaged host cells can activate different host responses that shape disease outcomes. Here, we show that mice and humans lacking a single allele of the DNA repair protein Ku70 had increased susceptibility to the development of intestinal cancer. Mechanistically, Ku70 translocates from the nucleus into the cytoplasm where it binds to cytosolic DNA and interacts with the GTPase Ras and the kinase Raf, forming a tripartite protein complex and docking at Rab5+ Rab7+ early-late endosomes...
January 26, 2024: Science Advances
https://read.qxmd.com/read/38253602/unexpected-inhibition-of-the-lipid-kinase-pikfyve-reveals-an-epistatic-role-for-p38-mapks-in-endolysosomal-fission-and-volume-control
#17
JOURNAL ARTICLE
Daric J Wible, Zalak Parikh, Eun Jeong Cho, Miao-Der Chen, Collene R Jeter, Somshuvra Mukhopadhyay, Kevin N Dalby, Shankar Varadarajan, Shawn B Bratton
p38 mitogen-activated protein kinases (MAPKs) participate in autophagic signaling; and previous reports suggest that pyridinyl imidazole p38 MAPK inhibitors, including SB203580 and SB202190, induce cell death in some cancer cell-types through unrestrained autophagy. Subsequent studies, however, have suggested that the associated cytoplasmic vacuolation resulted from off-target inhibition of an unidentified enzyme. Herein, we report that SB203580-induced vacuolation is rapid, reversible, and relies on the class III phosphatidylinositol 3-kinase (PIK3C3) complex and the production of phosphatidylinositol 3-phosphate [PI(3)P] but not on autophagy per se...
January 22, 2024: Cell Death & Disease
https://read.qxmd.com/read/38198575/loss-of-the-hops-complex-disrupts-early-to-late-endosome-transition-impairs-endosomal-recycling-and-induces-accumulation-of-amphisomes
#18
JOURNAL ARTICLE
Jan van der Beek, Cilia de Heus, Paolo Sanza, Nalan Liv, Judith Klumperman
The multisubunit HOPS tethering complex is a well-established regulator of lysosome fusion with late endosomes and autophagosomes. However, the role of the HOPS complex in other stages of endo-lysosomal trafficking is not well understood. To address this, we made HeLa cells knocked out for the HOPS-specific subunits Vps39 or Vps41, or the HOPS-CORVET-core subunits Vps18 or Vps11. In all four knockout cells we found that endocytosed cargos were trapped in enlarged endosomes that clustered in the perinuclear area...
January 10, 2024: Molecular Biology of the Cell
https://read.qxmd.com/read/38191051/akt1-is-involved-in-hcv-release-by-promoting-endoplasmic-reticulum-to-endosome-transition-of-infectious-virions
#19
JOURNAL ARTICLE
Wei-Ping Lee, Shi-Xian Liao, Yi-Hsiang Huang, Ming-Chih Hou, Keng-Hsin Lan
AIMS: Hepatitis C virus (HCV) relies on the viral and host factors to complete its life cycle. It has evolved to profit from Akt activation at some stage in its life cycle through various mechanisms, notably by activating lipogenesis, which is crucial for infectious virions production. MATERIALS AND METHODS: By employing an Akt-specific inhibitor, the impact of Akt on intracellular and extracellular infectivity was investigated. To ascertain the role of Akt in the HCV life cycle, the two-part cell culture-derived HCV infection protocol utilizing Akt1 small interfering RNAs (siRNAs) was implemented...
January 6, 2024: Life Sciences
https://read.qxmd.com/read/38172666/key-roles-of-autophagosome-endosome-maturation-mediated-by-syntaxin17-in-methamphetamine-induced-neuronal-damage-in-mice
#20
JOURNAL ARTICLE
Xi Wang, Miaoyang Hu, Jingrong Chen, Xinyu Lou, Hongchao Zhang, Muhan Li, Jie Cheng, Tengfei Ma, Jianping Xiong, Rong Gao, Xufeng Chen, Jun Wang
BACKGROUND: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood. METHODS: To address the mechanism of Meth-induced cognitive impairment, the adenovirus (AV) and adeno-associated virus (AAV) were injected into the hippocampus for stereotaxis to overexpress Stx17 in vivo to examine the cognitive ability via morris water maze and novel object recognition...
January 3, 2024: Molecular Medicine
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