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JOURNAL ARTICLE
Hung-Hsi Chen, Hsin-I Yu, Jason Jie-Sheng Chang, Chia-Wei Li, Muh-Hwa Yang, Mien-Chie Hung, Woan-Yuh Tarn
Programmed death-1 (PD-1)/PD ligand-1 (PD-L1)-mediated immune escape contributes to cancer development and has been targeted as an anti-cancer strategy. Here, we show that inhibition of the RNA helicase DDX3 increased CD8+ T cell infiltration in syngeneic oral squamous cell carcinoma tumors. DDX3 knockdown compromised interferon-γ-induced PD-L1 expression and, in particular, reduced the level of cell-surface PD-L1. DDX3 promoted surface PD-L1 expression by recruiting the adaptor protein 2 (AP2) complex to the 3' UTR of PD-L1 mRNA...
March 13, 2024: Cell Reports
#2
JOURNAL ARTICLE
Owen Byford, Amelia B Shaw, Hiu Nam Tse, Eleanor J A A Todd, Beatriz Álvarez-Rodríguez, Roger Hewson, Juan Fontana, John N Barr
Lymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within the Arenaviridae family of the Bunyavirales order. LCMV is associated with fatal disease in immunocompromized populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within this group. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library...
February 9, 2024: Journal of Virology
#3
JOURNAL ARTICLE
Selket Delafontaine, Alberto Iannuzzo, Tarin M Bigley, Bram Mylemans, Ruchit R Rana, Pieter Baatsen, M Cecilia Poli, Daisy Rymen, Katrien Jansen, Djalila Mekahli, Ingele Casteels, Catherine Cassiman, Philippe Demaerel, Alice Lepelley, Marie-Louise Frémond, Rik Schrijvers, Xavier Bossuyt, Katlijn Vints, Wim Huybrechts, Rachida Tacine, Karen Willekens, Anniek Corveleyn, Bram Boeckx, Marco Baggio, Lisa Ehlers, Sebastian Munck, Diether Lambrechts, Arnout Rd Voet, Leen Moens, Giorgia Bucciol, Megan A Cooper, Carla M Davis, Jérôme Delon, Isabelle Meyts
Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis and nephritis. We described three heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C and p.R1142X) in six children from three unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of the coat protein complex I (COPI)...
January 4, 2024: Journal of Clinical Investigation
#4
JOURNAL ARTICLE
Chang Lu, Zhi-Feng Luo, Donge Tang, Fengping Zheng, Shanshan Li, Shizhen Liu, Jing Qiu, Fanna Liu, Yong Dai, Wei-Guo Sui, Qiang Yan
Idiopathic membranous nephropathy (IMN) is a common type of primary glomerulonephritis, which pathogenesis are highly involved protein and immune regulation. Therefore, we investigated protein expression in different microregions of the IMN kidney tissue. We used laser capture microdissection and mass spectrometry to identify the proteins in the kidney tissue. Using MSstats software to identify the differently expressed protein (DEP). Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to predict and enrich the potential functions of the DEPs, and DEPs were compared to the Public data in the gene expression omnibus (GEO) database for screening biomarkers of IMN...
December 15, 2023: Medicine (Baltimore)
#5
JOURNAL ARTICLE
Debajit Dey, Enya Qing, Yanan He, Yihong Chen, Benjamin Jennings, Whitaker Cohn, Suruchi Singh, Lokesh Gakhar, Nicholas J Schnicker, Brian G Pierce, Julian P Whitelegge, Balraj Doray, John Orban, Tom Gallagher, S Saif Hasan
The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion...
December 15, 2023: Nature Communications
#6
JOURNAL ARTICLE
Domhnall McHugh, Bin Sun, Carmen Gutierrez-Muñoz, Fernanda Hernández-González, Massimiliano Mellone, Romain Guiho, Imanol Duran, Joaquim Pombo, Federico Pietrocola, Jodie Birch, Wouter W Kallemeijn, Sanjay Khadayate, Gopuraja Dharmalingam, Santiago Vernia, Edward W Tate, Juan Pedro Martínez-Barbera, Dominic J Withers, Gareth J Thomas, Manuel Serrano, Jesús Gil
Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and unfolded protein response-dependent apoptosis of senescent cells, and knockdown of COPI subunits improves the outcomes of cancer and fibrosis in mouse models...
November 27, 2023: Nature Cell Biology
#7
JOURNAL ARTICLE
Yue Zheng, Yue Du, Yubin Wu, Fuwei Li, Weiyue Gu, Chengguang Zhao
BACKGROUND: COPA syndrome is a recently described and rare monogenic autosomal dominant disease caused by heterozygous missense mutations in the Coatomer Protein Subunit alpha (COPA) gene that encodes the alpha subunit of coat protein complex I (COPI). Its main clinical manifestations are inflammatory lung disease, arthritis, and renal disease. The development of inflammation in COPA syndrome maybe due to abnormal autophagic response and abnormal activation of type I interferon pathway...
October 25, 2023: Molecular Genetics & Genomic Medicine
#8
JOURNAL ARTICLE
Adam Wells, Cláudia C Mendes, Felix Castellanos, Phoebe Mountain, Tia Wright, S Mark Wainwright, M Irina Stefana, Adrian L Harris, Deborah C I Goberdhan, Clive Wilson
Secretory cells in glands and the nervous system frequently package and store proteins destined for regulated secretion in dense-core granules (DCGs), which disperse when released from the cell surface. Despite the relevance of this dynamic process to diseases such as diabetes and human neurodegenerative disorders, our mechanistic understanding is relatively limited, because of the lack of good cell models to follow the nanoscale events involved. Here, we employ the prostate-like secondary cells (SCs) of the Drosophila male accessory gland to dissect the cell biology and genetics of DCG biogenesis...
October 2023: PLoS Genetics
#9
JOURNAL ARTICLE
Kelsey M Haas, Michael J McGregor, Mehdi Bouhaddou, Benjamin J Polacco, Eun-Young Kim, Thong T Nguyen, Billy W Newton, Matthew Urbanowski, Heejin Kim, Michael A P Williams, Veronica V Rezelj, Alexandra Hardy, Andrea Fossati, Erica J Stevenson, Ellie Sukerman, Tiffany Kim, Sudhir Penugonda, Elena Moreno, Hannes Braberg, Yuan Zhou, Giorgi Metreveli, Bhavya Harjai, Tia A Tummino, James E Melnyk, Margaret Soucheray, Jyoti Batra, Lars Pache, Laura Martin-Sancho, Jared Carlson-Stevermer, Alexander S Jureka, Christopher F Basler, Kevan M Shokat, Brian K Shoichet, Leah P Shriver, Jeffrey R Johnson, Megan L Shaw, Sumit K Chanda, Dan M Roden, Tonia C Carter, Leah C Kottyan, Rex L Chisholm, Jennifer A Pacheco, Maureen E Smith, Steven J Schrodi, Randy A Albrecht, Marco Vignuzzi, Lorena Zuliani-Alvarez, Danielle L Swaney, Manon Eckhardt, Steven M Wolinsky, Kris M White, Judd F Hultquist, Robyn M Kaake, Adolfo García-Sastre, Nevan J Krogan
Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases...
September 27, 2023: Nature Communications
#10
JOURNAL ARTICLE
Amirmasoud Shiri, Hossein Jafari Khamirani, Neda Kamal, Jamal Manoochehri, Mehdi Dianatpour, Seyed Mohammad Bagher Tabei, Seyed Alireza Dastgheib
COPB2 gene encodes the Coatomer Protein Complex Subunit Beta-2 that plays a crucial role in the cellular vesicle transport system and it is essential for brain development during embryogenesis. Mutations in COPB2 lead to an extremely rare genetic disease named Microcephaly type 19 with autosomal recessive inheritance. This study describes a missense pathogenic homozygous variant (NM_004766.3:c.760 C > T, p.Arg254Cys) in the COPB2 gene, which was identified by Whole-Exome sequencing and confirmed by Sanger sequencing...
September 19, 2023: European Journal of Medical Genetics
#11
JOURNAL ARTICLE
Xenia Georgiou, Sofia Dimou, George Diallinas, Martina Samiotaki
Neosynthesized plasma membrane (PM) proteins co-translationally translocate to the ER, concentrate at regions called ER-exit sites (ERes) and pack into COPII secretory vesicles which are sorted to the early-Golgi through membrane fusion. Following Golgi maturation, membrane cargoes reach the late-Golgi, from where they exit in clathrin-coated vesicles destined to the PM, directly or through endosomes. Post-Golgi membrane cargo trafficking also involves the cytoskeleton and the exocyst. The Golgi-dependent secretory pathway is thought to be responsible for the trafficking of all major membrane proteins...
September 18, 2023: Fungal Genetics and Biology: FG&B
#12
JOURNAL ARTICLE
Yiğit Kaçar, Hasan Batmaz
BACKGROUND: Although there are studies on colostrum and milk proteomics of different species in the literature, there is no published report about different quality bovine colostrums' proteomics. OBJECTIVES: The aim of this study was to compare the proteome content of high- and low-quality bovine colostrums for the first time. METHODS: Colostrum samples were collected from 32 Holstein cows from the same farm that had just calved. Brix% levels of colostrums were measured, and then, those with a Brix% value of ≥27% were classified as high-quality and those with a Brix% value of <22% as low-quality...
November 2023: Veterinary Medicine and Science
#13
JOURNAL ARTICLE
Laura De Nardi, Marco Francesco Natale, Virginia Messia, Paolo Tomà, Fabrizio De Benedetti, Antonella Insalaco
BACKGROUND: Ataxia-telangiectasia (A-T) is a rare autosomal recessive DNA repair disorder, characterized by progressive cerebellar degeneration, telangiectasia, immunodeficiency, recurrent sinopulmonary infections, radiation sensitivity, premature aging and predisposition to cancer. Although the association with autoimmune and chronic inflammatory conditions such as vitiligo, thrombocytopenia and arthritis has occasionally been reported, an onset with articular involvement at presentation is rare...
September 4, 2023: Italian Journal of Pediatrics
#14
JOURNAL ARTICLE
Sara K Custer, Timra Gilson, Jacob W Astroski, Siddarth R Nanguneri, Alyssa M Iurillo, Elliot J Androphy
The COPI coatomer subunit α-COP has been shown to co-precipitate mRNA in multiple settings, but it was unclear whether the interaction with mRNA was direct or mediated by interaction with an adapter protein. The COPI complex often interacts with proteins via C-terminal dilysine domains. A search for candidate RNA binding proteins with C-terminal dilysine motifs yielded Nucleolin, which terminates in a KKxKxx sequence. This protein was an especially intriguing candidate as it has been identified as an interacting partner for Survival Motor Neuron protein (SMN)...
September 2, 2023: Human Molecular Genetics
#15
JOURNAL ARTICLE
Debajit Dey, S Saif Hasan
The vesicular secretion of soluble cargo proteins from the endoplasmic reticulum (ER) is accompanied by the export of ER-resident membrane proteins that are co-packaged in secretory vesicles. The cytosolic coatomer protein complex I (COPI) utilizes the N-terminal WD40 domains of α-COPI and β'-COPI subunits to bind these membrane protein "clients" for ER retrieval. These "αWD40" and "β'WD40" domains are structural homologs that demonstrate distinct selectivity for client proteins. However, elucidation of the atomic-level principles of coatomer-client interactions has been challenging due to the tendency of αWD40 domain to undergo aggregation during expression and purification...
August 23, 2023: Protein Expression and Purification
#16
Uxia Gurriaran-Rodriguez, David Datzkiw, Leandro G Radusky, Marie Esper, Fan Xiao, Hong Ming, Solomon Fisher, Marina A Rojas, Yves De Repentigny, Rashmi Kothary, Adriana L Rojas, Luis Serrano, Aitor Hierro, Michael A Rudnicki
Wnt proteins are secreted hydrophobic glycoproteins that act over long distances through poorly understood mechanisms. We discovered that Wnt7a is secreted on extracellular vesicles (EVs) following muscle injury. Structural analysis identified the motif responsible for Wnt7a secretion on EVs that we term the Exosome Binding Peptide (EBP). Addition of the EBP to an unrelated protein directed secretion on EVs. Disruption of palmitoylation, knockdown of WLS, or deletion of the N-terminal signal peptide did not affect Wnt7a secretion on purified EVs...
May 30, 2023: bioRxiv
#17
JOURNAL ARTICLE
Drahomíra Faktorová, Kristína Záhonová, Corinna Benz, Joel B Dacks, Mark C Field, Julius Lukeš
The β-propeller protein Sec13 plays roles in at least three distinct processes by virtue of being a component of the COPII endoplasmic reticulum export vesicle coat, the nuclear pore complex (NPC) and the Seh1-associated (SEA)/GATOR nutrient-sensing complex. This suggests that regulatory mechanisms coordinating these cellular activities may operate via Sec13. The NPC, COPII and SEA/GATOR are all ancient features of eukaryotic cells, and in the vast majority of eukaryotes, a single Sec13 gene is present...
June 2023: Open Biology
#18
JOURNAL ARTICLE
Anna Papierniak-Wyglądała, Weronika Lamch, Ewelina Jurewicz, Katarzyna A Nałęcz
l-carnitine is indispensable for transfer of fatty acids to mitochondria for the process of β-oxidation, a process, whose significance in cancer has drawn attention in recent years. In humans majority of carnitine is delivered by diet and enters the cell due to activity of solute carriers (SLCs), mainly by ubiquitously expressed organic cation/carnitine transporter (OCTN2/SLC22A5). In control and cancer human breast epithelial cell lines the major fraction of OCTN2 is present as a not matured non-glycosylated form...
May 13, 2023: Archives of Biochemistry and Biophysics
#19
JOURNAL ARTICLE
Ye Hong, Zengfei Xia, Yuting Sun, Yingxia Lan, Tian Di, Jing Yang, Jian Sun, Miaozhen Qiu, Qiuyun Luo, Dajun Yang
The Coatomer protein complex Zeta 1 (COPZ1) has been reported to play an essential role in maintaining the survival of some types of tumors. In this study, we sought to explore the molecular characteristics of COPZ1 and its clinical prognostic value through a pan-cancers bioinformatic analysis. We found that COPZ1 was extremely prevalent in a variety of cancer types, and high expression of COPZ1 was linked to poor overall survival in many cancers, while low expression in LAML and PADC was correlated with tumorigenesis...
April 10, 2023: Genes
#20
JOURNAL ARTICLE
Marisa Dilucca, Petr Broz
The non-canonical inflammasome pathway functions as the primary cytosolic innate immune detection mechanism for Gram-negative bacterial lipopolysaccharide (LPS) in human and mouse cells and controls the proteolytic activation of the cell death executor gasdermin D (GSDMD). The main effectors of this pathways are the inflammatory proteases caspase-11 in mice and caspase-4/caspase-5 in humans. These caspases have been shown to bind LPS directly; however, the interaction between LPS and caspase-4/caspase-11 requires a set of interferon (IFN)-inducible GTPases, known as guanylate-binding proteins (GBPs)...
2023: Methods in Molecular Biology
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