keyword
https://read.qxmd.com/read/38533500/alveolar-capillary-endocytosis-and-trafficking-in-acute-lung-injury-and-acute-respiratory-distress-syndrome
#1
REVIEW
Vitalii Kryvenko, István Vadász
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality but lacks specific therapeutic options. Diverse endocytic processes play a key role in all phases of acute lung injury (ALI), including the initial insult, development of respiratory failure due to alveolar flooding, as a consequence of altered alveolar-capillary barrier function, as well as in the resolution or deleterious remodeling after injury. In particular, clathrin-, caveolae-, endophilin- and glycosylphosphatidyl inositol-anchored protein-mediated endocytosis, as well as, macropinocytosis and phagocytosis have been implicated in the setting of acute lung damage...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38528836/spatial-temporal-mapping-reveals-the-golgi-as-the-major-processing-site-for-the-pathogenic-swedish-app-mutation-familial-app-mutant-shifts-the-major-app-processing-site
#2
JOURNAL ARTICLE
Jingqi Wang, Paul A Gleeson, Lou Fourriere
Alzheimer's disease is associated with increased levels of amyloid beta (Aβ) generated by sequential intracellular cleavage of amyloid precursor protein (APP) by membrane-bound secretases. However, the spatial and temporal APP cleavage events along the trafficking pathways are poorly defined. Here, we use the Retention Using Selective Hooks (RUSH) to compare in real time the anterograde trafficking and temporal cleavage events of wild-type APP (APPwt) with the pathogenic Swedish APP (APPswe) and the disease-protective Icelandic APP (APPice)...
March 2024: Traffic
https://read.qxmd.com/read/38527856/app-antisense-oligonucleotides-reduce-a%C3%AE-aggregation-and-rescue-endolysosomal-dysfunction-in-alzheimer-s-disease
#3
JOURNAL ARTICLE
Christy Hung, Emre Fertan, Frederick J Livesey, David Klenerman, Rickie Patani
APP gene dosage is strongly associated with Alzheimer's disease (AD) pathogenesis. Genomic duplication of the APP locus leads to autosomal dominant early-onset AD. Individuals with Down syndrome (trisomy of chromosome 21) harbor 3 copies of the APP gene and invariably develop progressive AD with highly characteristic neuropathological features. Restoring expression of APP to the equivalent of that of two gene copies, or lower, is a rational therapeutic strategy, as it would restore physiological levels of neuronal APP protein without the potentially deleterious consequences of inadvertently inducing loss of APP function...
March 25, 2024: Brain
https://read.qxmd.com/read/38516730/a-root-knot-nematode-effector-targets-the-arabidopsis-cysteine-protease-rd21a-for-degradation-to-suppress-plant-defense-and-promote-parasitism
#4
JOURNAL ARTICLE
Jiarong Yu, Qing Yuan, Chen Chen, Tianyu Xu, Yuwen Jiang, Wenjun Hu, Aolin Liao, Jiayi Zhang, Xiuhu Le, Hongmei Li, Xuan Wang
Meloidogyne incognita is one of the most widely distributed plant-parasitic nematodes and causes severe economic losses annually. The parasite produces effector proteins that play essential roles in successful parasitism. Here, we identified one such effector named MiCE108, which is exclusively expressed within the nematode subventral esophageal gland cells and is upregulated in the early parasitic stage of M. incognita. A yeast signal sequence trap assay showed that MiCE108 contains a functional signal peptide for secretion...
March 22, 2024: Plant Journal
https://read.qxmd.com/read/38509168/development-of-a-novel-aak1-inhibitor-via-kinobeads-based-screening
#5
JOURNAL ARTICLE
Akari Yoshida, Satomi Ohtsuka, Fumiya Matsumoto, Tomoyuki Miyagawa, Rei Okino, Yumeya Ikeda, Natsume Tada, Akira Gotoh, Masaki Magari, Naoya Hatano, Ryo Morishita, Ayano Satoh, Yukinari Sunatsuki, Ulf J Nilsson, Teruhiko Ishikawa, Hiroshi Tokumitsu
A chemical proteomics approach using Ca2+ /calmodulin-dependent protein kinase kinase (CaMKK) inhibitor-immobilized sepharose (TIM-063-Kinobeads) identified main targets such as CaMKKα/1 and β/2, and potential off-target kinases, including AP2-associated protein kinase 1 (AAK1), as TIM-063 interactants. Because TIM-063 interacted with the AAK1 catalytic domain and inhibited its enzymatic activity moderately (IC50  = 8.51 µM), we attempted to identify potential AAK1 inhibitors from TIM-063-derivatives and found a novel AAK1 inhibitor, TIM-098a (11-amino-2-hydroxy-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one) which is more potent (IC50  = 0...
March 20, 2024: Scientific Reports
https://read.qxmd.com/read/38509070/rab-gtpases-and-phosphoinositides-fine-tune-snares-dependent-targeting-specificity-of-intracellular-vesicle-traffic
#6
JOURNAL ARTICLE
Seiichi Koike, Reinhard Jahn
In the secretory pathway the destination of trafficking vesicles is determined by specific proteins that, with the notable exception of SNAREs, are recruited from soluble pools. Previously we have shown that microinjected proteoliposomes containing early or late endosomal SNAREs, respectively, are targeted to the corresponding endogenous compartments, with targeting specificity being dependent on the recruitment of tethering factors by some of the SNAREs. Here, we show that targeting of SNARE-containing liposomes is refined upon inclusion of polyphosphoinositides and Rab5...
March 20, 2024: Nature Communications
https://read.qxmd.com/read/38499154/kif5b-mediated-internalization-of-fmdv-promotes-virus-infection
#7
JOURNAL ARTICLE
Wei Zhang, Fan Yang, Yang Yang, Weijun Cao, Wenhua Shao, Jiali Wang, Mengyao Huang, Zhitong Chen, Xiaoyi Zhao, Weiwei Li, Zixiang Zhu, Haixue Zheng
Foot-and-mouth disease (FMD) is a highly contagious and economically important disease, that is caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this study, we found that kinesin family member 5B (KIF5B) plays a vital role during FMDV internalization. Moreover, we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation (Co-IP) and co-localization in FMDV-infected cells...
March 16, 2024: Virologica Sinica
https://read.qxmd.com/read/38496652/visualization-of-endogenous-g-proteins-on-endosomes-and-other-organelles
#8
Wonjo Jang, Kanishka Senarath, Sumin Lu, Nevin A Lambert
Classical G protein-coupled receptor (GPCR) signaling takes place in response to extracellular stimuli and involves receptors and heterotrimeric G proteins located at the plasma membrane. It has recently been established that GPCR signaling can also take place from intracellular membrane compartments, including endosomes that contain internalized receptors and ligands. While the mechanisms of GPCR endocytosis are well understood, it is not clear how internalized receptors are supplied with G proteins. To address this gap we use gene editing, confocal microscopy, and bioluminescence resonance energy transfer to study the distribution and trafficking of endogenous G proteins...
March 7, 2024: bioRxiv
https://read.qxmd.com/read/38487979/morpholinodiazenyl-chalcone-blocks-influenza-a-virus-capsid-uncoating-by-perturbing-the-clathrin-mediated-vesicular-trafficking-pathway
#9
JOURNAL ARTICLE
Ahammed A Thottasseri, Gaganpreet Kaur, Deepthi Ramesh, Indranil Banerjee, Tharanikkarasu Kannan
Influenza A virus (IAV) is a highly contagious respiratory pathogen that significantly threatens global health by causing seasonal epidemics and occasional, unpredictable pandemics. To identify new compounds with therapeutic potential against IAV, we designed and synthesized a series of 4'-morpholinodiazenyl chalcones using the molecular hybridization method, performed a high-content screen against IAV, and found that (E)-1-{4-[(E)-morpholinodiazenyl]phenyl}-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (MC-22) completely neutralized IAV infection...
March 15, 2024: Archiv der Pharmazie
https://read.qxmd.com/read/38485453/internalisation-of-neutrophils-extracellular-traps-by-macrophages-aggravate-rheumatoid-arthritis-via-rab5a
#10
JOURNAL ARTICLE
Haixin Ye, Qian Yang, Huaxia Guo, Xing Wang, Lifang Cheng, Bingqi Han, Mukeng Hong, Fopei Ma, Meng Li, Xianghui Wu, Feilong Chen, Junqing Zhu, Shixian Chen, Songyuan Zheng, Juan Li
OBJECTIVES: Although elevated levels of neutrophil extracellular traps (NETs) have been reported in patients with rheumatoid arthritis (RA), the role of NETs in RA and the relationship between NETs and macrophages in the pathogenesis of RA requires further research. Here, we sought to determine the role of NETs in RA pathogenesis and reveal the potential mechanism. METHODS: Neutrophil elastase (NE) and myeloperoxidase (MPO)-DNA were measured in human serum and synovium...
March 14, 2024: RMD Open
https://read.qxmd.com/read/38483999/distinct-early-role-of-pten-regulation-during-hcmv-infection-of-monocytes
#11
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/38483897/mechanisms-of-active-diffusion-of-vesicular-stomatitis-virus-inclusion-bodies-and-cellular-early-endosomes-in-the-cytoplasm-of-mammalian-cells
#12
JOURNAL ARTICLE
Steven J Moran, Ryan Oglietti, Kathleen C Smith, Jed C Macosko, George Holzwarth, Douglas S Lyles
Viral and cellular particles too large to freely diffuse have two different types of mobility in the eukaryotic cell cytoplasm: directed motion mediated by motor proteins moving along cytoskeletal elements with the particle as its load, and motion in random directions mediated by motor proteins interconnecting cytoskeletal elements. The latter motion is referred to as "active diffusion." Mechanisms of directed motion have been extensively studied compared to mechanisms of active diffusion, despite the observation that active diffusion is more common for many viral and cellular particles...
2024: PloS One
https://read.qxmd.com/read/38477472/comparison-of-sars-cov-2-variants-of-concern-in-primary-human-nasal-cultures-demonstrates-delta-as-most-cytopathic-and-omicron-as-fastest-replicating
#13
JOURNAL ARTICLE
Nikhila S Tanneti, Anant K Patel, Li Hui Tan, Andrew D Marques, Ranawaka A P M Perera, Scott Sherrill-Mix, Brendan J Kelly, David M Renner, Ronald G Collman, Kyle Rodino, Carole Lee, Frederic D Bushman, Noam A Cohen, Susan R Weiss
UNLABELLED: The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid interface were used to model upper respiratory infection and compared to cell lines derived from human lung epithelia. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency...
March 13, 2024: MBio
https://read.qxmd.com/read/38474321/the-chd-protein-kismet-restricts-the-synaptic-localization-of-cell-adhesion-molecules-at-the-drosophila-neuromuscular-junction
#14
JOURNAL ARTICLE
Ireland R Smith, Emily L Hendricks, Nina K Latcheva, Daniel R Marenda, Faith L W Liebl
The appropriate expression and localization of cell surface cell adhesion molecules must be tightly regulated for optimal synaptic growth and function. How neuronal plasma membrane proteins, including cell adhesion molecules, cycle between early endosomes and the plasma membrane is poorly understood. Here we show that the Drosophila homolog of the chromatin remodeling enzymes CHD7 and CHD8, Kismet, represses the synaptic levels of several cell adhesion molecules. Neuroligins 1 and 3 and the integrins αPS2 and βPS are increased at kismet mutant synapses but Kismet only directly regulates transcription of neuroligin 2 ...
March 6, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473798/-ehrlichia-chaffeensis-etf-3-induces-host-rab15-upregulation-for-bacterial-intracellular-growth
#15
JOURNAL ARTICLE
Nan Yang, Meifang Li, Shanhua Qin, Nan Duan, Xiaoxiao Li, Yuhong Zhou, Mengyao Wang, Yongxin Jin, Weihui Wu, Zhihui Cheng
Ehrlichia chaffeensis infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, E. chaffeensis resides in membrane-bound inclusions, E. chaffeensis -containing vesicles (ECVs), which have early endosome-like characteristics and fuse with early autophagosomes but not lysosomes, to evade host innate immune microbicidal mechanisms and obtain nutrients for bacterial intracellular growth. The mechanisms exploited by E. chaffeensis to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied...
February 22, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38464287/the-loss-of-opa1-accelerates-intervertebral-disc-degeneration-and-osteoarthritis-in-aged-mice
#16
Makarand Risbud, Vedavathi Madhu, Miriam Hernandez-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, John Collins
NP cells of the intervertebral disc and articular chondrocytes reside in avascular and hypoxic tissue niches. As a consequence of these environmental constraints the cells are primarily glycolytic in nature and were long thought to have a minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues. However, the foundational understanding of mechanisms governing mitochondrial dynamics and function in these tissues is lacking...
February 20, 2024: Research Square
https://read.qxmd.com/read/38451235/the-ion-channels-of-endomembranes
#17
REVIEW
Meiqin Hu, Xinghua Feng, Qiang Liu, Siyu Liu, Fangqian Huang, Haoxing Xu
The endomembrane system consists of organellar membranes in the biosynthetic pathway: endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles, as well as those in the degradative pathway: early endosomes, macropinosomes, phagosomes, autophagosomes, late endosomes, and lysosomes. These endomembrane organelles/vesicles work together to synthesize, modify, package, transport, and degrade proteins, carbohydrates, and lipids, regulating the balance between cellular anabolism and catabolism. Large ion concentration gradients exist across endomembranes - Ca2+ gradients for most endomembrane organelles and H+ gradients for the acidic compartments...
March 7, 2024: Physiological Reviews
https://read.qxmd.com/read/38448164/genome-scale-requirements-for-dynein-based-transport-revealed-by-a-high-content-arrayed-crispr-screen
#18
JOURNAL ARTICLE
Chun Hao Wong, Steven W Wingett, Chen Qian, Morag Rose Hunter, J Matthew Taliaferro, Douglas Ross-Thriepland, Simon L Bullock
The microtubule motor dynein plays a key role in cellular organization. However, little is known about how dynein's biosynthesis, assembly, and functional diversity are orchestrated. To address this issue, we have conducted an arrayed CRISPR loss-of-function screen in human cells using the distribution of dynein-tethered peroxisomes and early endosomes as readouts. From a genome-wide gRNA library, 195 validated hits were recovered and parsed into those impacting multiple dynein cargoes and those whose effects are restricted to a subset of cargoes...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38447793/swedish-alzheimer-s-disease-variant-perturbs-activity-of-retrograde-molecular-motors-and-causes-widespread-derangement-of-axonal-transport-pathways
#19
JOURNAL ARTICLE
Monica Feole, Victorio M Pozo Devoto, Neda Dragišić, Cayetana Arnaiz, Julieta Bianchelli, Kateřina Texlová, Kristina Kovačovicova, Jan S Novotny, Daniel Havas, Tomas L Falzone, Gorazd B Stokin
Experimental studies in flies, mice, and humans suggest a significant role of impaired axonal transport in the pathogenesis of Alzheimer's disease (AD). The mechanisms underlying these impairments in axonal transport, however, remain poorly understood. Here we report that the Swedish familial AD mutation causes a standstill of the Amyloid Precursor Protein (APP) in the axons at the expense of its reduced anterograde transport. The standstill reflects the perturbed directionality of the axonal transport of APP, which spends significantly more time traveling in the retrograde direction...
March 4, 2024: Journal of Biological Chemistry
https://read.qxmd.com/read/38423010/bi-allelic-variants-in-snf8-cause-a-disease-spectrum-ranging-from-severe-developmental-and-epileptic-encephalopathy-to-syndromic-optic-atrophy
#20
JOURNAL ARTICLE
Melanie Brugger, Antonella Lauri, Yan Zhen, Laura L Gramegna, Benedikt Zott, Nikolina Sekulić, Giulia Fasano, Robert Kopajtich, Viviana Cordeddu, Francesca Clementina Radio, Cecilia Mancini, Simone Pizzi, Graziamaria Paradisi, Ginevra Zanni, Gessica Vasco, Rosalba Carrozzo, Flavia Palombo, Caterina Tonon, Raffaele Lodi, Chiara La Morgia, Maria Arelin, Cristiane Blechschmidt, Tom Finck, Vigdis Sørensen, Kornelia Kreiser, Gertrud Strobl-Wildemann, Hagit Daum, Rachel Michaelson-Cohen, Lucia Ziccardi, Giuseppe Zampino, Holger Prokisch, Rami Abou Jamra, Claudio Fiorini, Thomas Arzberger, Juliane Winkelmann, Leonardo Caporali, Valerio Carelli, Harald Stenmark, Marco Tartaglia, Matias Wagner
The endosomal sorting complex required for transport (ESCRT) machinery is essential for membrane remodeling and autophagy and it comprises three multi-subunit complexes (ESCRT I-III). We report nine individuals from six families presenting with a spectrum of neurodevelopmental/neurodegenerative features caused by bi-allelic variants in SNF8 (GenBank: NM_007241.4), encoding the ESCRT-II subunit SNF8. The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy, massive reduction of white matter, hypo-/aplasia of the corpus callosum, neurodevelopmental arrest, and early death...
February 21, 2024: American Journal of Human Genetics
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