Traffic最新文献_第10页

The trans-SNARE complex VAMP4/Stx6/Stx7/Vti1b is a key regulator of Golgi to late endosome MT1-MMP transport in macrophages. 跨snare复合物VAMP4/Stx6/Stx7/Vti1b是巨噬细胞中高尔基体到晚期核内体MT1-MMP运输的关键调节因子。

IF 4.5 3区生物学

Traffic Pub Date : 2021-11-01 Epub Date: 2021-09-13 DOI: 10.1111/tra.12813

Zoe Elizabeth West, Savannah Margaret Aitcheson, Annalese Barbara Trudy Semmler, Rachael Zoe Murray

{"title":"The trans-SNARE complex VAMP4/Stx6/Stx7/Vti1b is a key regulator of Golgi to late endosome MT1-MMP transport in macrophages.","authors":"Zoe Elizabeth West, Savannah Margaret Aitcheson, Annalese Barbara Trudy Semmler, Rachael Zoe Murray","doi":"10.1111/tra.12813","DOIUrl":"https://doi.org/10.1111/tra.12813","url":null,"abstract":"The activity of the matrix metalloproteinase (MMP) MT1-MMP is strictly regulated by expression and cellular location. In macrophages LPS activation leads to the up-regulation of MT1-MMP and this need to be at the cell surface for them to degrade the dense extracellular matrix (ECM) components to create a path to migrate into injured and infected tissues. Fixed and live imaging shows newly made MT1-MMP is packaged into vesicles that traffic to and fuse with LBPA+ LAMP1+ late endosomes en route to the surface. The R-SNARE VAMP4, found on Golgi-derived vesicles that traffic to late endosomes, forms a trans-SNARE complex with the Q-SNARE complex Stx6/Stx7/Vti1b. The Stx6/Stx7/Vti1b complex has been shown to be up-regulated in lipopolysaccharide (LPS)-activated cells to increase trafficking of key cytokines through the classical pathway and now we show here it is up-regulation also plays a role in the late endosomal pathway of MT1-MMP trafficking. Depletion of any of the SNAREs in this complex reduces surface MT1-MMP and gelatin degradation. Conversely, overexpression of the Stx6/Stx7/Vti1b components increases surface MT1-MMP levels. This suggests that Stx6/Stx7/Vti1b is a key Q-SNARE complex in macrophages during an immune response and in partnership with VAMP4 it regulates transport of newly made MT1-MMP.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 11","pages":"368-376"},"PeriodicalIF":4.5,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39380588","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}

引用次数: 3

Fur4-mediated uracil-scavenging to screen for surface protein regulators. Fur4介导的尿嘧啶清除以筛选表面蛋白调节因子。

IF 4.5 3区生物学

Traffic Pub Date : 2021-11-01 Epub Date: 2021-09-23 DOI: 10.1111/tra.12815

Katherine M Paine, Gabrielle B Ecclestone, Chris MacDonald

{"title":"Fur4-mediated uracil-scavenging to screen for surface protein regulators.","authors":"Katherine M Paine, Gabrielle B Ecclestone, Chris MacDonald","doi":"10.1111/tra.12815","DOIUrl":"https://doi.org/10.1111/tra.12815","url":null,"abstract":"Cell surface membrane proteins perform diverse and critical functions and are spatially and temporally regulated by membrane trafficking pathways. Although perturbations in these pathways underlie many pathologies, our understanding of these pathways at a mechanistic level remains incomplete. Using yeast as a model, we have developed an assay that reports on the surface activity of the uracil permease Fur4 in uracil auxotroph strains grown in the presence of limited uracil. This assay was used to screen a library of haploid deletion strains and identified mutants with both diminished and enhanced comparative growth in restricted uracil media. Factors identified, including various multisubunit complexes, were enriched for membrane trafficking and transcriptional functions, in addition to various uncharacterized genes. Bioinformatic analysis of expression profiles from many strains lacking transcription factors required for efficient uracil-scavenging validated particular hits from the screen, in addition to implicating essential genes not tested in the screen. Finally, we performed a secondary mating factor secretion screen to functionally categorize factors implicated in uracil-scavenging.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 11","pages":"397-408"},"PeriodicalIF":4.5,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39397432","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}

引用次数: 2

Late endosomal/lysosomal accumulation of a neurotransmitter receptor in a cellular model of Smith-Lemli-Opitz syndrome. Smith-Lemli-Opitz综合征细胞模型中神经递质受体晚期内体/溶酶体积累。

IF 4.5 3区生物学

Traffic Pub Date : 2021-10-01 Epub Date: 2021-08-27 DOI: 10.1111/tra.12811

Ashwani Sharma, G Aditya Kumar, Amitabha Chattopadhyay

{"title":"Late endosomal/lysosomal accumulation of a neurotransmitter receptor in a cellular model of Smith-Lemli-Opitz syndrome.","authors":"Ashwani Sharma, G Aditya Kumar, Amitabha Chattopadhyay","doi":"10.1111/tra.12811","DOIUrl":"https://doi.org/10.1111/tra.12811","url":null,"abstract":"Smith-Lemli-Opitz syndrome (SLOS) is a congenital and developmental malformation syndrome associated with defective cholesterol biosynthesis. It is characterized by accumulation of 7-dehydrocholesterol (the immediate biosynthetic precursor of cholesterol in the Kandutsch-Russell pathway) and an altered cholesterol to total sterol ratio. Because SLOS is associated with neurological malfunction, exploring the function and trafficking of neuronal receptors and their interaction with membrane lipids under these conditions assume significance. In this work, we generated a cellular model of SLOS in HEK-293 cells stably expressing the human serotonin1A receptor (an important neurotransmitter G-protein coupled receptor) using AY 9944, an inhibitor for the enzyme 3β-hydroxy-steroid-∆7 -reductase (7-DHCR). Using a quantitative flow cytometry based assay, we show that the plasma membrane population of serotonin1A receptors was considerably reduced under these conditions without any change in total cellular expression of the receptor. Interestingly, the receptors were trafficked to sterol-enriched LysoTracker positive compartments, which accumulated under these conditions. To the best of our knowledge, our results constitute one of the first reports demonstrating intracellular accumulation and misregulated traffic of a neurotransmitter GPCR in SLOS-like conditions. We believe these results assume relevance in our overall understanding of the molecular basis underlying the functional relevance of neurotransmitter receptors in SLOS.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 10","pages":"332-344"},"PeriodicalIF":4.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39331487","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}

引用次数: 9

Phosphatidic acid-PKA signaling regulates p38 and ERK1/2 functions in ligand-independent EGFR endocytosis. 磷脂酸- pka信号调节p38和ERK1/2在不依赖配体的EGFR内吞作用中的功能。

IF 4.5 3区生物学

Traffic Pub Date : 2021-10-01 DOI: 10.1111/tra.12812

Claudia Metz, Claudia Oyanadel, Juan Jung, Claudio Retamal, Jorge Cancino, Jonathan Barra, Jaime Venegas, Guangwei Du, Andrea Soza, Alfonso González

{"title":"Phosphatidic acid-PKA signaling regulates p38 and ERK1/2 functions in ligand-independent EGFR endocytosis.","authors":"Claudia Metz, Claudia Oyanadel, Juan Jung, Claudio Retamal, Jorge Cancino, Jonathan Barra, Jaime Venegas, Guangwei Du, Andrea Soza, Alfonso González","doi":"10.1111/tra.12812","DOIUrl":"https://doi.org/10.1111/tra.12812","url":null,"abstract":"Ligand-independent epidermal growth factor receptor (EGFR) endocytosis is inducible by a variety of stress conditions converging upon p38 kinase. A less known pathway involves phosphatidic acid (PA) signaling toward the activation of type 4 phosphodiesterases (PDE4) that decrease cAMP levels and protein kinase A (PKA) activity. This PA/PDE4/PKA pathway is triggered with propranolol used to inhibit PA hydrolysis and induces clathrin-dependent and clathrin-independent endocytosis, followed by reversible accumulation of EGFR in recycling endosomes. Here we give further evidence of this signaling pathway using biosensors of PA, cAMP, and PKA in live cells and then show that it activates p38 and ERK1/2 downstream the PKA inhibition. Clathrin-silencing and IN/SUR experiments involved the activity of p38 in the clathrin-dependent route, while ERK1/2 mediates clathrin-independent EGFR endocytosis. The PA/PDE4/PKA pathway selectively increases the EGFR endocytic rate without affecting LDLR and TfR constitute endocytosis. This selectiveness is probably because of EGFR phosphorylation, as detected in Th1046/1047 and Ser669 residues. The EGFR accumulates at perinuclear recycling endosomes colocalizing with TfR, fluorescent transferrin, and Rab11, while a small proportion distributes to Alix-endosomes. A non-selective recycling arrest includes LDLR and TfR in a reversible manner. The PA/PDE4/PKA pathway involving both p38 and ERK1/2 expands the possibilities of EGFR transmodulation and interference in cancer.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 10","pages":"345-361"},"PeriodicalIF":4.5,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39342407","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}

引用次数: 3

RNA, a new member in the glycan-club that gets exposed at the cell surface. RNA，聚糖俱乐部的新成员暴露在细胞表面。

IF 4.5 3区生物学

Traffic Pub Date : 2021-10-01 Epub Date: 2021-08-17 DOI: 10.1111/tra.12810

Eric Chevet, Maria Antonietta De Matteis, Eeva-Liisa Eskelinen, Hesso Farhan

引用次数: 3

Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi? 沿神经元分泌途径产生β淀粉样蛋白:高尔基体的危险联系?

IF 4.5 3区生物学

Traffic Pub Date : 2021-09-01 Epub Date: 2021-07-11 DOI: 10.1111/tra.12808

Lou Fourriere, Paul A Gleeson

引用次数: 9

Sequence-based features that are determinant for tail-anchored membrane protein sorting in eukaryotes. 真核生物中决定尾锚膜蛋白分选的序列特征。

IF 4.5 3区生物学

Traffic Pub Date : 2021-09-01 Epub Date: 2021-08-03 DOI: 10.1111/tra.12809

Michelle Y Fry, Shyam M Saladi, Alexandre Cunha, William M Clemons

{"title":"Sequence-based features that are determinant for tail-anchored membrane protein sorting in eukaryotes.","authors":"Michelle Y Fry, Shyam M Saladi, Alexandre Cunha, William M Clemons","doi":"10.1111/tra.12809","DOIUrl":"10.1111/tra.12809","url":null,"abstract":"The correct targeting and insertion of tail-anchored (TA) integral membrane proteins is critical for cellular homeostasis. TA proteins are defined by a hydrophobic transmembrane domain (TMD) at their C-terminus and are targeted to either the ER or mitochondria. Derived from experimental measurements of a few TA proteins, there has been little examination of the TMD features that determine localization. As a result, the localization of many TA proteins are misclassified by the simple heuristic of overall hydrophobicity. Because ER-directed TMDs favor arrangement of hydrophobic residues to one side, we sought to explore the role of geometric hydrophobic properties. By curating TA proteins with experimentally determined localizations and assessing hypotheses for recognition, we bioinformatically and experimentally verify that a hydrophobic face is the most accurate singular metric for separating ER and mitochondria-destined yeast TA proteins. A metric focusing on an 11 residue segment of the TMD performs well when classifying human TA proteins. The most inclusive predictor uses both hydrophobicity and C-terminal charge in tandem. This work provides context for previous observations and opens the door for more detailed mechanistic experiments to determine the molecular factors driving this recognition.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 9","pages":"306-318"},"PeriodicalIF":4.5,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380732/pdf/nihms-1726178.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39205172","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}

引用次数: 0

Dynamic, variable oligomerization and the trafficking of variant surface glycoproteins of Trypanosoma brucei. 布鲁氏锥虫动态、可变寡聚化和不同表面糖蛋白的转运。

IF 4.5 3区生物学

Traffic Pub Date : 2021-08-01 Epub Date: 2021-06-29 DOI: 10.1111/tra.12806

Khan Umaer, Francisco Aresta-Branco, Monica Chandra, Monique van Straaten, Johan Zeelen, Karine Lapouge, Brandon Waxman, C Erec Stebbins, James D Bangs

{"title":"Dynamic, variable oligomerization and the trafficking of variant surface glycoproteins of Trypanosoma brucei.","authors":"Khan Umaer, Francisco Aresta-Branco, Monica Chandra, Monique van Straaten, Johan Zeelen, Karine Lapouge, Brandon Waxman, C Erec Stebbins, James D Bangs","doi":"10.1111/tra.12806","DOIUrl":"https://doi.org/10.1111/tra.12806","url":null,"abstract":"African trypanosomes cause disease in humans and livestock, avoiding host immunity by changing the expression of variant surface glycoproteins (VSGs); the major glycosylphosphatidylinositol (GPI) anchored antigens coating the surface of the bloodstream stage. Proper trafficking of VSGs is therefore critical to pathogen survival. The valence model argues that GPI anchors regulate progression and fate in the secretory pathway and that, specifically, a valence of two (VSGs are dimers) is critical for stable cell surface association. However, recent reports that the MITat1.3 (M1.3) VSG N-terminal domain (NTD) behaves as a monomer in solution and in a crystal structure challenge this model. We now show that the behavior of intact M1.3 VSG in standard in vivo trafficking assays is consistent with an oligomer. Nevertheless, Blue Native Gel electrophoresis and size exclusion chromatography-multiangle light scattering chromatography of purified full length M1.3 VSG indicates a monomer in vitro. However, studies with additional VSGs show that multiple oligomeric states are possible, and that for some VSGs oligomerization is concentration dependent. These data argue that individual VSG monomers possess different propensities to self-oligomerize, but that when constrained at high density to the cell surface, oligomeric species predominate. These results resolve the apparent conflict between the valence hypothesis and the M1.3 NTD VSG crystal structure.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 8","pages":"274-283"},"PeriodicalIF":4.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12806","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39073890","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}

引用次数: 4

The ESCRT-III complex contributes to macromitophagy in yeast. ESCRT-III复合体有助于酵母的巨噬细胞。

IF 4.5 3区生物学

Traffic Pub Date : 2021-08-01 Epub Date: 2021-06-16 DOI: 10.1111/tra.12805

Zulin Wu, Haiqian Xu, Junze Liu, Fan Zhou, Yongheng Liang

{"title":"The ESCRT-III complex contributes to macromitophagy in yeast.","authors":"Zulin Wu, Haiqian Xu, Junze Liu, Fan Zhou, Yongheng Liang","doi":"10.1111/tra.12805","DOIUrl":"https://doi.org/10.1111/tra.12805","url":null,"abstract":"Mitochondria play important roles in energy generation and homeostasis maintenance in eukaryotic cells. The damaged or superfluous mitochondria can be nonselectively or selectively removed through the autophagy/lysosome pathway, which was referred as mitophagy. According to the molecular machinery for degrading mitochondria, the selectively removed mitochondria can occur through macromitophagy or micromitophagy. In this study, we show that the endosomal sorting complex required for transport III (ESCRT-III) in budding yeast regulates macromitophagy induced by nitrogen starvation, but not by the post-logarithmic phase growth in lactate medium by monitoring a mitochondrial marker, Om45. Firstly, loss of ESCRT-III subunit Snf7 or Vps4-Vta1 complex subunit Vps4, two representative subunits of the ESCRT complex, suppresses the delivery and degradation of Om45-GFP to vacuoles. Secondly, we show that the mitochondrial marker Om45 and mitophagy receptor Atg32 accumulate on autophagosomes marked with Atg8 (mitophagosomes, MPs) in ESCRT mutants. Moreover, the protease-protection assay indicates that Snf7 and Vps4 are involved in MP closure. Finally, Snf7 interacts with Atg11, which was detected by two ways, glutathione-S-transferase (GST) pulldown and bimolecular fluorescence complementation (BiFC) assay, and this BiFC interaction happens on mitochondrial reticulum. Therefore, we proposed that the ESCRT-III machinery mediates nitrogen starvation-induced macromitophagy by the interaction between Snf7 and Atg11 so that Snf7 is recruited to Atg32-marked MPs by the known Atg11-Atg32 interaction to seal them. These results reveal that the ESCRT-III complex plays a new role in yeast on macromitophagy.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 8","pages":"258-273"},"PeriodicalIF":4.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39079307","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}

引用次数: 3

Legionella pneumophila LegC7 effector protein drives aberrant endoplasmic reticulum:endosome contacts in yeast. 嗜肺军团菌LegC7效应蛋白驱动异常内质网:酵母内体接触。

IF 4.5 3区生物学

Traffic Pub Date : 2021-08-01 Epub Date: 2021-07-07 DOI: 10.1111/tra.12807

Nathan K Glueck, Kevin M O'Brien, Danielle C Seguin, Vincent J Starai

{"title":"Legionella pneumophila LegC7 effector protein drives aberrant endoplasmic reticulum:endosome contacts in yeast.","authors":"Nathan K Glueck, Kevin M O'Brien, Danielle C Seguin, Vincent J Starai","doi":"10.1111/tra.12807","DOIUrl":"https://doi.org/10.1111/tra.12807","url":null,"abstract":"Legionella pneumophila is a facultative intracellular bacterial pathogen, causing the severe form of pneumonia known as Legionnaires' disease. Legionella actively alters host organelle trafficking through the activities of \"effector\" proteins secreted via a type-IVB secretion system, in order to construct the bacteria-laden Legionella-containing vacuole (LCV) and prevent lysosomal degradation. The LCV is created with membrane derived from host endoplasmic reticulum (ER), secretory vesicles and phagosomes, although the precise molecular mechanisms that drive its synthesis remain poorly understood. In an effort to characterize the in vivo activity of the LegC7/YlfA SNARE-like effector protein from Legionella in the context of eukaryotic membrane trafficking in yeast, we find that LegC7 interacts with the Emp46p/Emp47p ER-to-Golgi glycoprotein cargo adapter complex, alters ER morphology and induces aberrant ER:endosome interactions, as measured by visualization of ER cargo degradation, reconstitution of split-GFP proteins and enhanced oxidation of the ER lumen. LegC7-dependent toxicity, disruption of ER morphology and ER:endosome fusion events were dependent upon endosomal VPS class C tethering complexes and the endosomal t-SNARE, Pep12p. This work establishes a model in which LegC7 functions to recruit host ER material to the bacterial phagosome during infection by driving ER:endosome contacts, potentially through interaction with host membrane tethering complexes and/or cargo adapters.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"22 8","pages":"284-302"},"PeriodicalIF":4.5,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/tra.12807","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39037682","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}

引用次数: 2