TrafficPub Date : 2023-03-01DOI: 10.1111/tra.12835
Clàudia Río-Bergé, Yingying Cong, Fulvio Reggiori
{"title":"Getting on the right track: Interactions between viruses and the cytoskeletal motor proteins.","authors":"Clàudia Río-Bergé, Yingying Cong, Fulvio Reggiori","doi":"10.1111/tra.12835","DOIUrl":"https://doi.org/10.1111/tra.12835","url":null,"abstract":"<p><p>The cytoskeleton is an essential component of the cell and it is involved in multiple physiological functions, including intracellular organization and transport. It is composed of three main families of proteinaceous filaments; microtubules, actin filaments and intermediate filaments and their accessory proteins. Motor proteins, which comprise the dynein, kinesin and myosin superfamilies, are a remarkable group of accessory proteins that mainly mediate the intracellular transport of cargoes along with the cytoskeleton. Like other cellular structures and pathways, viruses can exploit the cytoskeleton to promote different steps of their life cycle through associations with motor proteins. The complexity of the cytoskeleton and the differences among viruses, however, has led to a wide diversity of interactions, which in most cases remain poorly understood. Unveiling the details of these interactions is necessary not only for a better comprehension of specific infections, but may also reveal new potential drug targets to fight dreadful diseases such as rabies disease and acquired immunodeficiency syndrome (AIDS). In this review, we describe a few examples of the mechanisms that some human viruses, that is, rabies virus, adenovirus, herpes simplex virus, human immunodeficiency virus, influenza A virus and papillomavirus, have developed to hijack dyneins, kinesins and myosins.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 3","pages":"114-130"},"PeriodicalIF":4.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-03-01Epub Date: 2022-12-30DOI: 10.1111/tra.12877
Stephen M Rawlinson, Tianyue Zhao, Katie Ardipradja, Yilin Zhang, Patrick F Veugelers, Jennifer A Harper, Cassandra T David, Vinod Sundaramoorthy, Gregory W Moseley
{"title":"Henipaviruses and lyssaviruses target nucleolar treacle protein and regulate ribosomal RNA synthesis.","authors":"Stephen M Rawlinson, Tianyue Zhao, Katie Ardipradja, Yilin Zhang, Patrick F Veugelers, Jennifer A Harper, Cassandra T David, Vinod Sundaramoorthy, Gregory W Moseley","doi":"10.1111/tra.12877","DOIUrl":"10.1111/tra.12877","url":null,"abstract":"<p><p>The nucleolus is a common target of viruses and viral proteins, but for many viruses the functional outcomes and significance of this targeting remains unresolved. Recently, the first intranucleolar function of a protein of a cytoplasmically-replicating negative-sense RNA virus (NSV) was identified, with the finding that the matrix (M) protein of Hendra virus (HeV) (genus Henipavirus, family Paramyxoviridae) interacts with Treacle protein within nucleolar subcompartments and mimics a cellular mechanism of the nucleolar DNA-damage response (DDR) to suppress ribosomal RNA (rRNA) synthesis. Whether other viruses utilise this mechanism has not been examined. We report that sub-nucleolar Treacle targeting and modulation is conserved between M proteins of multiple Henipaviruses, including Nipah virus and other potentially zoonotic viruses. Furthermore, this function is also evident for P3 protein of rabies virus, the prototype virus of a different RNA virus family (Rhabdoviridae), with Treacle depletion in cells also found to impact virus production. These data indicate that unrelated proteins of viruses from different families have independently developed nucleolar/Treacle targeting function, but that modulation of Treacle has distinct effects on infection. Thus, subversion of Treacle may be an important process in infection by diverse NSVs, and so could provide novel targets for antiviral approaches with broad specificity.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 3","pages":"146-157"},"PeriodicalIF":4.5,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of cholesterol transport impairs Cav-1 trafficking and small extracellular vesicles secretion, promoting amphisome formation in melanoma cells.","authors":"Daniela Peruzzu, Zaira Boussadia, Federica Fratini, Francesca Spadaro, Lucia Bertuccini, Massimo Sanchez, Maria Carollo, Paola Matarrese, Mario Falchi, Francesca Iosi, Carla Raggi, Isabella Parolini, Alessandra Carè, Massimo Sargiacomo, Maria Cristina Gagliardi, Katia Fecchi","doi":"10.1111/tra.12878","DOIUrl":"https://doi.org/10.1111/tra.12878","url":null,"abstract":"<p><p>Caveolin-1 (Cav-1) is a fundamental constituent of caveolae, whose functionality and structure are strictly dependent on cholesterol. In this work the U18666A inhibitor was used to study the role of cholesterol transport in the endosomal degradative-secretory system in a metastatic human melanoma cell line (WM266-4). We found that U18666A induces a shift of Cav-1 from the plasma membrane to the endolysosomal compartment, which is involved, through Multi Vesicular Bodies (MVBs), in the formation and release of small extracellular vesicles (sEVs). Moreover, this inhibitor induces an increase in the production of sEVs with chemical-physical characteristics similar to control sEVs but with a different protein composition (lower expression of Cav-1 and increase of LC3II) and reduced transfer capacity on target cells. Furthermore, we determined that U18666A affects mitochondrial function and also cancer cell aggressive features, such as migration and invasion. Taken together, these results indicate that the blockage of cholesterol transport, determining the internalization of Cav-1, may modify sEVs secretory pathways through an increased fusion between autophagosomes and MVBs to form amphisome, which in turn fuses with the plasma membrane releasing a heterogeneous population of sEVs to maintain homeostasis and ensure correct cellular functionality.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 2","pages":"76-94"},"PeriodicalIF":4.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10612069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-02-01Epub Date: 2022-12-15DOI: 10.1111/tra.12876
Farhana Taher Sumya, Irina D Pokrovskaya, Zinia D'Souza, Vladimir V Lupashin
{"title":"Acute COG complex inactivation unveiled its immediate impact on Golgi and illuminated the nature of intra-Golgi recycling vesicles.","authors":"Farhana Taher Sumya, Irina D Pokrovskaya, Zinia D'Souza, Vladimir V Lupashin","doi":"10.1111/tra.12876","DOIUrl":"10.1111/tra.12876","url":null,"abstract":"<p><p>Conserved Oligomeric Golgi (COG) complex controls Golgi trafficking and glycosylation, but the precise COG mechanism is unknown. The auxin-inducible acute degradation system was employed to investigate initial defects resulting from COG dysfunction. We found that acute COG inactivation caused a massive accumulation of COG-dependent (CCD) vesicles that carry the bulk of Golgi enzymes and resident proteins. v-SNAREs (GS15, GS28) and v-tethers (giantin, golgin84, and TMF1) were relocalized into CCD vesicles, while t-SNAREs (STX5, YKT6), t-tethers (GM130, p115), and most of Rab proteins remained Golgi-associated. Airyscan microscopy and velocity gradient analysis revealed that different Golgi residents are segregated into different populations of CCD vesicles. Acute COG depletion significantly affected three Golgi-based vesicular coats-COPI, AP1, and GGA, suggesting that COG uniquely orchestrates tethering of multiple types of intra-Golgi CCD vesicles produced by different coat machineries. This study provided the first detailed view of primary cellular defects associated with COG dysfunction in human cells.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 2","pages":"52-75"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/0a/TRA-24-52.PMC9969905.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9366380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolic depletion of sphingolipids inhibits agonist-induced endocytosis of the serotonin<sub>1A</sub> receptor.","authors":"Abhishek Kumar, Parijat Sarkar, Amitabha Chattopadhyay","doi":"10.1111/tra.12879","DOIUrl":"https://doi.org/10.1111/tra.12879","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are vital cellular signaling machinery and currently represent ~40% drug targets. Endocytosis of GPCRs is an important process that allows stringent spatiotemporal control over receptor population on the cell surface. Although the role of proteins in GPCR endocytosis is well addressed, the contribution of membrane lipids in this process is rather unexplored. Sphingolipids are essential functional lipids in higher eukaryotes and are implicated in several neurological functions. To understand the role of sphingolipids in GPCR endocytosis, we subjected cells expressing human serotonin<sub>1A</sub> receptors (an important neurotransmitter GPCR involved in cognitive and behavioral functions) to metabolic sphingolipid depletion using fumonisin B<sub>1</sub> , an inhibitor of sphingolipid biosynthetic pathway. Our results, using flow cytometric analysis and confocal microscopic imaging, show that sphingolipid depletion inhibits agonist-induced endocytosis of the serotonin<sub>1A</sub> receptor in a concentration-dependent manner, which was restored when sphingolipid levels were replenished. We further show that there was no change in the internalization of transferrin, a marker for clathrin-mediated endocytosis, under sphingolipid-depleted condition, highlighting the specific requirement of sphingolipids for endocytosis of serotonin<sub>1A</sub> receptors. Our results reveal the regulatory role of sphingolipids in GPCR endocytosis and highlight the importance of neurotransmitter receptor trafficking in health and disease.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 2","pages":"95-107"},"PeriodicalIF":4.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10588330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-01-01Epub Date: 2022-12-13DOI: 10.1111/tra.12875
Lauren Kustigian, Xue Gong, Wei Gai, Jirapat Thongchol, Junjie Zhang, Jason Puchalla, Chavela M Carr, Hays S Rye
{"title":"GTP-stimulated membrane fission by the N-BAR protein AMPH-1.","authors":"Lauren Kustigian, Xue Gong, Wei Gai, Jirapat Thongchol, Junjie Zhang, Jason Puchalla, Chavela M Carr, Hays S Rye","doi":"10.1111/tra.12875","DOIUrl":"10.1111/tra.12875","url":null,"abstract":"<p><p>Membrane-enclosed transport carriers sort biological molecules between stations in the cell in a dynamic process that is fundamental to the physiology of eukaryotic organisms. While much is known about the formation and release of carriers from specific intracellular membranes, the mechanism of carrier formation from the recycling endosome, a compartment central to cellular signaling, remains to be resolved. In Caenorhabditis elegans, formation of transport carriers from the recycling endosome requires the dynamin-like, Eps15-homology domain (EHD) protein, RME-1, functioning with the Bin/Amphiphysin/Rvs (N-BAR) domain protein, AMPH-1. Here we show, using a free-solution single-particle technique known as burst analysis spectroscopy (BAS), that AMPH-1 alone creates small, tubular-vesicular products from large, unilamellar vesicles by membrane fission. Membrane fission requires the amphipathic H0 helix of AMPH-1 and is slowed in the presence of RME-1. Unexpectedly, AMPH-1-induced membrane fission is stimulated in the presence of GTP. Furthermore, the GTP-stimulated membrane fission activity seen for AMPH-1 is recapitulated by the heterodimeric N-BAR amphiphysin protein from yeast, Rvs161/167p, strongly suggesting that GTP-stimulated membrane fission is a general property of this important class of N-BAR proteins.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 1","pages":"34-47"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9081605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.","authors":"Qi-Xin Wen, Biao-Luo, Xiao-Yong Xie, Gui-Feng Zhou, Jian Chen, Li Song, Shi-Qi Xie, Long Chen, Kun-Yi Li, Xiao-Jiao Xiang, Guo-Jun Chen","doi":"10.1111/tra.12874","DOIUrl":"https://doi.org/10.1111/tra.12874","url":null,"abstract":"<p><p>AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic β-amyloid peptide (Aβ). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aβ in cells stably expressing human full-length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9-positive late endosomes (LE) to LAMP1-positive lysosomes, which was paralleled by the enhanced LE-lysosome fusion. In support, silencing of vacuolar protein sorting-associated protein 41 (VPS41) that is implicated in LE-lyso fusion prevented AP2S1-mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV-mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aβ, with the concomitant APP translocalization, LE-lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE-lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 1","pages":"20-33"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2b/fb/TRA-24-20.PMC10107530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9319839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2023-01-01DOI: 10.1111/tra.12873
Mai Ly Tran, Johanna Tüshaus, Yeongho Kim, Bulat R Ramazanov, Swathi Devireddy, Stefan F Lichtenthaler, Shawn M Ferguson, Julia von Blume
{"title":"Cab45 deficiency leads to the mistargeting of progranulin and prosaposin and aberrant lysosomal positioning.","authors":"Mai Ly Tran, Johanna Tüshaus, Yeongho Kim, Bulat R Ramazanov, Swathi Devireddy, Stefan F Lichtenthaler, Shawn M Ferguson, Julia von Blume","doi":"10.1111/tra.12873","DOIUrl":"10.1111/tra.12873","url":null,"abstract":"<p><p>The trans-Golgi Network (TGN) sorts molecular \"addresses\" and sends newly synthesized proteins to their destination via vesicular transport carriers. Despite the functional significance of packaging processes at the TGN, the sorting of soluble proteins remains poorly understood. Recent research has shown that the Golgi resident protein Cab45 is a significant regulator of secretory cargo sorting at the TGN. Cab45 oligomerizes upon transient Ca<sup>2+</sup> influx, recruits soluble cargo molecules (clients), and packs them in sphingomyelin-rich transport carriers. However, the identity of client molecules packed into Cab45 vesicles is scarce. Therefore, we used a precise and highly efficient secretome analysis technology called hiSPECs. Intriguingly, we observed that Cab45 deficient cells manifest hypersecretion of lysosomal hydrolases. Specifically, Cab45 deficient cells secrete the unprocessed precursors of prosaposin (PSAP) and progranulin (PGRN). In addition, lysosomes in these cells show an aberrant perinuclear accumulation suggesting a new role of Cab45 in lysosomal positioning. This work uncovers a yet unknown function of Cab45 in regulating lysosomal function.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 1","pages":"4-19"},"PeriodicalIF":4.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9134689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
TrafficPub Date : 2022-12-01Epub Date: 2022-10-24DOI: 10.1111/tra.12870
Tanja Petnicki-Ocwieja, Bijaya Sharma, Urmila Powale, Devesh Pathak, Shumin Tan, Linden T Hu
{"title":"An AP-3-dependent pathway directs phagosome fusion with Rab8 and Rab11 vesicles involved in TLR2 signaling.","authors":"Tanja Petnicki-Ocwieja, Bijaya Sharma, Urmila Powale, Devesh Pathak, Shumin Tan, Linden T Hu","doi":"10.1111/tra.12870","DOIUrl":"10.1111/tra.12870","url":null,"abstract":"<p><p>Intracellular compartmentalization of ligands, receptors and signaling molecules has been recognized as an important regulator of inflammation. The toll-like receptor (TLR) 2 pathway utilizes the trafficking molecule adaptor protein 3 (AP-3) to activate interleukin (IL)-6 signaling from within phagosomal compartments. To better understand the vesicular pathways that may contribute to intracellular signaling and cooperate with AP-3, we performed a vesicular siRNA screen. We identified Rab8 and Rab11 GTPases as important in IL-6 induction upon stimulation with the TLR2 ligand Pam<sub>3</sub> CSK<sub>4</sub> or the pathogen, Borrelia burgdorferi (Bb), the causative agent of Lyme disease. These Rabs were recruited to late and lysosomal stage phagosomes and co-transported with TLR2 signaling adaptors and effectors, such as MyD88, TRAM and TAK1, in an AP-3-dependent manner. Our data support a model where AP-3 mediates the recruitment of recycling and secretory vesicles and the assembly of signaling complexes at the phagosome.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 12","pages":"558-567"},"PeriodicalIF":4.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10757455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}