Traffic最新文献 - Book学术

Acute GARP Depletion Disrupts Vesicle Transport, Leading to Severe Defects in Sorting, Secretion and O-Glycosylation.

IF 3.6 3区生物学

Traffic Pub Date : 2025-01-01 DOI: 10.1111/tra.70003

Amrita Khakurel, Irina Pokrovskaya, Walter S Aragon-Ramirez, Vladimir V Lupashin

{"title":"Acute GARP Depletion Disrupts Vesicle Transport, Leading to Severe Defects in Sorting, Secretion and O-Glycosylation.","authors":"Amrita Khakurel, Irina Pokrovskaya, Walter S Aragon-Ramirez, Vladimir V Lupashin","doi":"10.1111/tra.70003","DOIUrl":"10.1111/tra.70003","url":null,"abstract":"The GARP complex is an evolutionarily conserved protein complex proposed to tether endosome-derived vesicles at the trans-Golgi network. While complete depletion of the GARP leads to severe trafficking and glycosylation defects, the primary defects linked to GARP dysfunction remain unclear. In this study, we utilized the mAID degron strategy to achieve rapid degradation of VPS54 in human cells, acutely disrupting GARP function. This resulted in the partial mislocalization and degradation of a subset of Golgi-resident proteins, including TGN46, ATP7A, TMEM87A, CPD, C1GALT1 and GS15. Enzyme recycling defects led to O-glycosylation abnormalities. Additionally, while fibronectin and cathepsin D secretion were altered, mannose-6-phosphate receptors were largely unaffected. Partial displacement of COPI, AP1 and GGA coats caused a significant accumulation of vesicle-like structures and large vacuoles. Electron microscopy detection of GARP-dependent vesicles and identifying specific cargo proteins provide direct experimental evidence of GARP's role as a vesicular tether. We conclude that the primary defects of GARP dysfunction involve vesicular coat mislocalization, accumulation of GARP-dependent vesicles, degradation and mislocalization of specific Golgi proteins and O-glycosylation defects.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70003"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658677","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

Adaptor-Mediated Trafficking of Tank Binding Kinase 1 During Diverse Cellular Processes.

IF 3.6 3区生物学

Traffic Pub Date : 2025-01-01 DOI: 10.1111/tra.70000

Swagatika Paul, Sahitya Ranjan Biswas, Julia P Milner, Porter L Tomsick, Alicia M Pickrell

引用次数: 0

Disease-Associated Factors at the Endoplasmic Reticulum-Golgi Interface.

IF 3.6 3区生物学

Traffic Pub Date : 2025-01-01 DOI: 10.1111/tra.70001

Miharu Maeda, Masashi Arakawa, Kota Saito

引用次数: 0

Computational Modeling Reveals a Catch-and-Guide Interaction Between Kinesin-1 and Tubulin C-Terminal Tails.

IF 3.6 3区生物学

Traffic Pub Date : 2025-01-01 DOI: 10.1111/tra.70002

Trini Nguyen, Steven P Gross, Christopher E Miles

{"title":"Computational Modeling Reveals a Catch-and-Guide Interaction Between Kinesin-1 and Tubulin C-Terminal Tails.","authors":"Trini Nguyen, Steven P Gross, Christopher E Miles","doi":"10.1111/tra.70002","DOIUrl":"https://doi.org/10.1111/tra.70002","url":null,"abstract":"The delivery of intracellular cargoes by kinesins is modulated at scales ranging from the geometry of the microtubule networks down to interactions with individual tubulins and their code. The complexity of the tubulin code and the difficulty in directly observing motor-tubulin interactions have hindered progress in pinpointing the precise mechanisms by which kinesin's function is modulated. As one such example, past experiments show that cleaving tubulin C-terminal tails (CTTs) lowers kinesin-1's processivity and velocity on microtubules, but how these CTTs intertwine with kinesin's processive cycle remains unclear. In this work, we formulate and interrogate several plausible mechanisms by which CTTs contribute to and modulate kinesin motion. Computational modeling bridges the gap between effective transport observations (processivity, velocities) and microscopic mechanisms. Ultimately, we find that a guiding mechanism can best explain the observed differences in processivity and velocity. Altogether, our work adds a new understanding of how the CTTs and their modulation via the tubulin code may steer intracellular traffic in both health and disease.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 1-3","pages":"e70002"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617257","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: 0

PcloC-Mediated Phase Separation in Short-Distance Vesicle Transport.

IF 3.6 3区生物学

Traffic Pub Date : 2024-11-01 DOI: 10.1111/tra.12959

Huyong Yan, Yixuan Deng

引用次数: 0

Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes. 用于监测和量化自噬、异噬和溶酶体转运通量的荧光报告器、成像和人工智能工具包。

IF 3.6 3区生物学

Traffic Pub Date : 2024-10-01 DOI: 10.1111/tra.12957

Mikhail Rudinskiy, Diego Morone, Maurizio Molinari

{"title":"Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes.","authors":"Mikhail Rudinskiy, Diego Morone, Maurizio Molinari","doi":"10.1111/tra.12957","DOIUrl":"https://doi.org/10.1111/tra.12957","url":null,"abstract":"Lysosomal compartments control the clearance of cell-own material (autophagy) or of material that cells endocytose from the external environment (heterophagy) to warrant supply of nutrients, to eliminate macromolecules or parts of organelles present in excess, aged, or containing toxic material. Inherited or sporadic mutations in lysosomal proteins and enzymes may hamper their folding in the endoplasmic reticulum (ER) and their lysosomal transport via the Golgi compartment, resulting in lysosomal dysfunction and storage disorders. Defective cargo delivery to lysosomal compartments is harmful to cells and organs since it causes accumulation of toxic compounds and defective organellar homeostasis. Assessment of resident proteins and cargo fluxes to the lysosomal compartments is crucial for the mechanistic dissection of intracellular transport and catabolic events. It might be combined with high-throughput screenings to identify cellular, chemical, or pharmacological modulators of these events that may find therapeutic use for autophagy-related and lysosomal storage disorders. Here, discuss qualitative, quantitative and chronologic monitoring of autophagic, heterophagic and lysosomal protein trafficking in fixed and live cells, which relies on fluorescent single and tandem reporters used in combination with biochemical, flow cytometry, light and electron microscopy approaches implemented by artificial intelligence-based technology.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 10","pages":"e12957"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508701","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: 0

Dissociation of Drosophila Evi-Wg Complex Occurs Post Apical Internalization in the Maturing Acidic Endosomes. 果蝇 Evi-Wg 复合物在成熟的酸性内体中发生顶端内化后解离

IF 3.6 3区生物学

Traffic Pub Date : 2024-09-01 DOI: 10.1111/tra.12955

Satyam Sharma, Varun Chaudhary

{"title":"Dissociation of Drosophila Evi-Wg Complex Occurs Post Apical Internalization in the Maturing Acidic Endosomes.","authors":"Satyam Sharma, Varun Chaudhary","doi":"10.1111/tra.12955","DOIUrl":"10.1111/tra.12955","url":null,"abstract":"Signaling pathways activated by secreted Wnt ligands play an essential role in tissue development and the progression of diseases, like cancer. Secretion of the lipid-modified Wnt proteins is tightly regulated by a repertoire of intracellular factors. For instance, a membrane protein, Evi, interacts with the Wnt ligand in the ER, and it is essential for its further trafficking and release in the extracellular space. After dissociating from the Wnt, the Wnt-unbound Evi is recycled back to the ER via Golgi. However, where in this trafficking path Wnt proteins dissociate from Evi remains unclear. Here, we have used the Drosophila wing epithelium to trace the route of the Evi-Wg (Wnt homolog) complex leading up to their separation. In these polarized cells, Wg is first trafficked to the apical surface; however, the secretion of Wg is believed to occurs post-internalization via recycling. Our results show that the Evi-Wg complex is internalized from the apical surface and transported to the retromer-positive endosomes. Furthermore, using antibodies that specifically label the Wnt-unbound Evi, we show that Evi and Wg separation occurs post-internalization in the acidic endosomes. These results refine our understanding of the polarized trafficking of Wg and highlight the importance of Wg endocytosis in its secondary secretion.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 9","pages":"e12955"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308628","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: 0

Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells. 转录后调控 Rab7a 在营养有限的癌细胞溶酶体定位和抗药性中的作用

IF 3.6 3区生物学

Traffic Pub Date : 2024-09-01 DOI: 10.1111/tra.12956

Aliye Ezgi Güleç Taşkıran, Hepşen H Hüsnügil, Zahra E Soltani, Göksu Oral, Nazlı S Menemenli, Chuanpit Hampel, Kerstin Huebner, Katharina Erlenbach-Wuensch, Ilir Sheraj, Regine Schneider-Stock, Aytekin Akyol, Nalan Liv, Sreeparna Banerjee

{"title":"Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells.","authors":"Aliye Ezgi Güleç Taşkıran, Hepşen H Hüsnügil, Zahra E Soltani, Göksu Oral, Nazlı S Menemenli, Chuanpit Hampel, Kerstin Huebner, Katharina Erlenbach-Wuensch, Ilir Sheraj, Regine Schneider-Stock, Aytekin Akyol, Nalan Liv, Sreeparna Banerjee","doi":"10.1111/tra.12956","DOIUrl":"10.1111/tra.12956","url":null,"abstract":"Limited nutrient availability in the tumor microenvironment can cause the rewiring of signaling and metabolic networks to confer cancer cells with survival advantages. We show here that the limitation of glucose, glutamine and serum from the culture medium resulted in the survival of a population of cancer cells with high viability and capacity to form tumors in vivo. These cells also displayed a remarkable increase in the abundance and size of lysosomes. Moreover, lysosomes were located mainly in the perinuclear region in nutrient-limited cells; this translocation was mediated by a rapid post-transcriptional increase in the key endolysosomal trafficking protein Rab7a. The acidic lysosomes in nutrient-limited cells could trap weakly basic drugs such as doxorubicin, mediating resistance of the cells to the drug, which could be partially reversed with the lysosomal inhibitor bafilomycin A1. An in vivo chorioallantoic membrane (CAM) assay indicated a remarkable decrease in microtumor volume when nutrient-limited cells were treated with 5-Fluorouracil (5-FU) and bafilomycin A1 compared to cells treated with either agent alone. Overall, our data indicate the activation of complementary pathways with nutrient limitation that can enable cancer cells to survive, proliferate and acquire drug resistance.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 9","pages":"e12956"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308629","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: 0

Intercellular Mitochondrial Transfer: The Novel Therapeutic Mechanism for Diseases. 细胞间线粒体转移：新的疾病治疗机制。

IF 3.6 3区生物学

Traffic Pub Date : 2024-09-01 DOI: 10.1111/tra.12951

Huimei Liu, Hui Mao, Xueqian Ouyang, Ruirui Lu, Lanfang Li

引用次数: 0

Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways. 对一种古老腺病毒前体蛋白 VII 的机理研究显示了多种核导入受体途径。

IF 3.6 3区生物学

Traffic Pub Date : 2024-09-01 DOI: 10.1111/tra.12953

Sepehr Nematollahzadeh, Ajani Athukorala, Camilla M Donnelly, Silvia Pavan, Victoria Atelie-Djossou, Enzo Di Iorio, Babu Nath, Karla J Helbig, Brian P McSharry, Jade K Forwood, Subir Sarker, Gualtiero Alvisi

{"title":"Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways.","authors":"Sepehr Nematollahzadeh, Ajani Athukorala, Camilla M Donnelly, Silvia Pavan, Victoria Atelie-Djossou, Enzo Di Iorio, Babu Nath, Karla J Helbig, Brian P McSharry, Jade K Forwood, Subir Sarker, Gualtiero Alvisi","doi":"10.1111/tra.12953","DOIUrl":"https://doi.org/10.1111/tra.12953","url":null,"abstract":"Adenoviral pVII proteins are multifunctional, highly basic, histone-like proteins that can bind to and transport the viral genome into the host cell nucleus. Despite the identification of several nuclear localization signals (NLSs) in the pVII protein of human adenovirus (HAdV)2, the mechanistic details of nuclear transport are largely unknown. Here we provide a full characterization of the nuclear import of precursor (Pre-) pVII protein from an ancient siadenovirus, frog siadenovirus 1 (FrAdV1), using a combination of structural, functional, and biochemical approaches. Two strong NLSs (termed NLSa and NLSd) interact with importin (IMP)β1 and IMPα, respectively, and are the main drivers of nuclear import. A weaker NLS (termed NLSb) also contributes, together with an additional signal (NLSc) which we found to be important for nucleolar targeting and intranuclear binding. Expression of wild-type and NLS defective derivatives Pre-pVII in the presence of selective inhibitors of different nuclear import pathways revealed that, unlike its human counterpart, FrAdV1 Pre-pVII nuclear import is dependent on IMPα/β1 and IMPβ1, but not on transportin-1 (IMPβ2). Clearly, AdVs evolved to maximize the nuclear import pathways for the pVII proteins, whose subcellular localization is the result of a complex process. Therefore, our results pave the way for an evolutionary comparison of the interaction of different AdVs with the host cell nuclear transport machinery.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 9","pages":"e12953"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296225","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: 0