Traffic最新文献 - Book学术

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

Intracellular Trafficking Defects in Congenital Intestinal and Hepatic Diseases. 先天性肠道和肝脏疾病中的细胞内运输缺陷。

IF 3.6 3区生物学

Traffic Pub Date : 2024-08-01 DOI: 10.1111/tra.12954

Luca Szabó, Adam R Pollio, Georg Friedrich Vogel

{"title":"Intracellular Trafficking Defects in Congenital Intestinal and Hepatic Diseases.","authors":"Luca Szabó, Adam R Pollio, Georg Friedrich Vogel","doi":"10.1111/tra.12954","DOIUrl":"https://doi.org/10.1111/tra.12954","url":null,"abstract":"Enterocytes and liver cells fulfill important metabolic and barrier functions and are responsible for crucial vectorial secretive and absorptive processes. To date, genetic diseases affecting metabolic enzymes or transmembrane transporters in the intestine and the liver are better comprehended than mutations affecting intracellular trafficking. In this review, we explore the emerging knowledge on intracellular trafficking defects and their clinical manifestations in both the intestine and the liver. We provide a detailed overview including more investigated diseases such as the canonical, variant and associated forms of microvillus inclusion disease, as well as recently described pathologies, highlighting the complexity and disease relevance of several trafficking pathways. We give examples of how intracellular trafficking hubs, such as the apical recycling endosome system, the trans-Golgi network, lysosomes, or the Golgi-to-endoplasmic reticulum transport are involved in the pathomechanism and lead to disease. Ultimately, understanding these processes could spark novel therapeutic approaches, which would greatly improve the quality of life of the affected patients.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 8","pages":"e12954"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073935","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

SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway. SNX32 调控活化表皮生长因子受体向溶酶体降解途径的排序和迁移

IF 3.6 3区生物学

Traffic Pub Date : 2024-07-01 DOI: 10.1111/tra.12952

Dou Wang, Xia Zhao, Panpan Wang, Jia-Jia Liu

引用次数: 0

Rab GTPases, Active Members in Antigen-Presenting Cells, and T Lymphocytes. Rab GTPases，抗原递呈细胞和 T 淋巴细胞中的活跃成员。

IF 3.6 3区生物学

Traffic Pub Date : 2024-06-01 DOI: 10.1111/tra.12950

Nidia Carolina Moreno-Corona, Mercedes Piedad de León-Bautista, Moises León-Juárez, Araceli Hernández-Flores, Juan Carlos Barragán-Gálvez, Orestes López-Ortega

引用次数: 0

EFA6A, an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells. EFA6A是Arf6的一种交换因子，它调控PC12细胞中依赖于NGF的TrkA从早期内体循环和神经元生长。

IF 4.5 3区生物学

Traffic Pub Date : 2024-05-01 DOI: 10.1111/tra.12936

Masahiro Fukaya, Kanta Ibuchi, Takeyuki Sugawara, Makoto Itakura, Akiko Ito, Tomoko Shiroshima, Yoshinobu Hara, Hirotsugu Okamoto, Frédéric Luton, Hiroyuki Sakagami

{"title":"EFA6A, an Exchange Factor for Arf6, Regulates NGF-Dependent TrkA Recycling From Early Endosomes and Neurite Outgrowth in PC12 Cells.","authors":"Masahiro Fukaya, Kanta Ibuchi, Takeyuki Sugawara, Makoto Itakura, Akiko Ito, Tomoko Shiroshima, Yoshinobu Hara, Hirotsugu Okamoto, Frédéric Luton, Hiroyuki Sakagami","doi":"10.1111/tra.12936","DOIUrl":"10.1111/tra.12936","url":null,"abstract":"Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 5","pages":"e12936"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899567","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

Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging. 载脂蛋白 E2 表达会改变衰老过程中脑外泌体水平升高的小鼠模型的内泌体通路

IF 4.5 3区生物学

Traffic Pub Date : 2024-05-01 DOI: 10.1111/tra.12937

Katherine Y Peng, Braison Liemisa, Jonathan Pasato, Pasquale D'Acunzo, Monika Pawlik, Adriana Heguy, Sai C Penikalapati, Amanda Labuza, Harshitha Pidikiti, Melissa J Alldred, Stephen D Ginsberg, Efrat Levy, Paul M Mathews

{"title":"Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging.","authors":"Katherine Y Peng, Braison Liemisa, Jonathan Pasato, Pasquale D'Acunzo, Monika Pawlik, Adriana Heguy, Sai C Penikalapati, Amanda Labuza, Harshitha Pidikiti, Melissa J Alldred, Stephen D Ginsberg, Efrat Levy, Paul M Mathews","doi":"10.1111/tra.12937","DOIUrl":"10.1111/tra.12937","url":null,"abstract":"The polymorphic APOE gene is the greatest genetic determinant of sporadic Alzheimer's disease risk: the APOE4 allele increases risk, while the APOE2 allele is neuroprotective compared with the risk-neutral APOE3 allele. The neuronal endosomal system is inherently vulnerable during aging, and APOE4 exacerbates this vulnerability by driving an enlargement of early endosomes and reducing exosome release in the brain of humans and mice. We hypothesized that the protective effects of APOE2 are, in part, mediated through the endosomal pathway. Messenger RNA analyses showed that APOE2 leads to an enrichment of endosomal pathways in the brain when compared with both APOE3 and APOE4. Moreover, we show age-dependent alterations in the recruitment of key endosomal regulatory proteins to vesicle compartments when comparing APOE2 to APOE3. In contrast to the early endosome enlargement previously shown in Alzheimer's disease and APOE4 models, we detected similar morphology and abundance of early endosomes and retromer-associated vesicles within cortical neurons of aged APOE2 targeted-replacement mice compared with APOE3. Additionally, we observed increased brain extracellular levels of endosome-derived exosomes in APOE2 compared with APOE3 mice during aging, consistent with enhanced endosomal cargo clearance by exosomes to the extracellular space. Our findings thus demonstrate that APOE2 enhances an endosomal clearance pathway, which has been shown to be impaired by APOE4 and which may be protective due to APOE2 expression during brain aging.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"25 5","pages":"e12937"},"PeriodicalIF":4.5,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080979","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