Traffic最新文献

{"title":"Developmental program-independent secretory granule degradation in larval salivary gland cells of Drosophila.","authors":"Tamás Csizmadia,&nbsp;Anna Dósa,&nbsp;Erika Farkas,&nbsp;Belián Valentin Csikos,&nbsp;Eszter Adél Kriska,&nbsp;Gábor Juhász,&nbsp;Péter Lőw","doi":"10.1111/tra.12871","DOIUrl":"https://doi.org/10.1111/tra.12871","url":null,"abstract":"<p><p>Both constitutive and regulated secretion require cell organelles that are able to store and release the secretory cargo. During development, the larval salivary gland of Drosophila initially produces high amount of glue-containing small immature secretory granules, which then fuse with each other and reach their normal 3-3.5 μm in size. Following the burst of secretion, obsolete glue granules directly fuse with late endosomes or lysosomes by a process called crinophagy, which leads to fast degradation and recycling of the secretory cargo. However, hindering of endosome-to-TGN retrograde transport in these cells causes abnormally small glue granules which are not able to fuse with each other. Here, we show that loss of function of the SNARE genes Syntaxin 16 (Syx16) and Synaptobrevin (Syb), the small GTPase Rab6 and the GARP tethering complex members Vps53 and Scattered (Vps54) all involved in retrograde transport cause intense early degradation of immature glue granules via crinophagy independently of the developmental program. Moreover, silencing of these genes also provokes secretory failure and accelerated crinophagy during larval development. Our results provide a better understanding of the relations among secretion, secretory granule maturation and degradation and paves the way for further investigation of these connections in other metazoans.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 12","pages":"568-586"},"PeriodicalIF":4.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10099382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9291067","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":"Multiplexed cellular profiling identifies an organoselenium compound as an inhibitor of CRM1-mediated nuclear export.","authors":"Lucia Jimenez,&nbsp;Victor Mayoral-Varo,&nbsp;Carlos Amenábar,&nbsp;Judit Ortega,&nbsp;João G N Sequeira,&nbsp;Miguel Machuqueiro,&nbsp;Cristiana Mourato,&nbsp;Romano Silvestri,&nbsp;Andrea Angeli,&nbsp;Fabrizio Carta,&nbsp;Claudiu T Supuran,&nbsp;Diego Megías,&nbsp;Bibiana I Ferreira,&nbsp;Wolfgang Link","doi":"10.1111/tra.12872","DOIUrl":"https://doi.org/10.1111/tra.12872","url":null,"abstract":"<p><p>Chromosomal region maintenance 1 (CRM1 also known as Xpo1 and exportin-1) is the receptor for the nuclear export controlling the intracellular localization and function of many cellular and viral proteins that play a crucial role in viral infections and cancer. The inhibition of CRM1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses, for the treatment of cancer, and to overcome therapy resistance. Recently, selinexor has been approved as the first CRM1 inhibitor for the treatment of multiple myeloma, providing proof of concept for this therapeutic option with a new mode of action. However, selinexor is associated with dose-limiting toxicity and hence, the discovery of alternative small molecule leads that could be developed as less toxic anticancer and antiviral therapeutics will have a significant impact in the clinic. Here, we report a CRM1 inhibitor discovery platform. The development of this platform includes reporter cell lines that monitor CRM1 activity by using red fluorescent protein or green fluorescent protein-labeled HIV-1 Rev protein with a strong heterologous nuclear export signal. Simultaneously, the intracellular localization of other proteins, to be interrogated for their capacity to undergo CRM1-mediated export, can be followed by co-culturing stable cell lines expressing fluorescent fusion proteins. We used this platform to interrogate the mode of nuclear export of several proteins, including PDK1, p110α, STAT5A, FOXO1, 3, 4 and TRIB2, and to screen a compound collection. We show that while p110α partially relies on CRM1-dependent nuclear export, TRIB2 is exported from the nucleus in a CRM1-independent manner. Compound screening revealed the striking activity of an organoselenium compound on the CRM1 nuclear export receptor.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 12","pages":"587-599"},"PeriodicalIF":4.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/b8/TRA-23-587.PMC10099545.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9291068","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":"Roles of long noncoding RNAs and small extracellular vesicle-long noncoding RNAs in type 2 diabetes.","authors":"Wenguang Chang,&nbsp;Man Wang,&nbsp;Yuan Zhang,&nbsp;Fei Yu,&nbsp;Bin Hu,&nbsp;Katarzyna Goljanek-Whysall,&nbsp;Peifeng Li","doi":"10.1111/tra.12868","DOIUrl":"https://doi.org/10.1111/tra.12868","url":null,"abstract":"<p><p>The prevalence of a high-energy diet and a sedentary lifestyle has increased the incidence of type 2 diabetes (T2D). T2D is a chronic disease characterized by high blood glucose levels and insulin resistance in peripheral tissues. The pathological mechanism of this disease is not fully clear. Accumulated evidence has shown that noncoding RNAs have an essential regulatory role in the progression of diabetes and its complications. The roles of small noncoding RNAs, such as miRNAs, in T2D, have been extensively investigated, while the function of long noncoding RNAs (lncRNAs) in T2D has been unstudied. It has been reported that lncRNAs in T2D play roles in the regulation of pancreatic function, peripheral glucose homeostasis and vascular inflammation. In addition, lncRNAs carried by small extracellular vesicles (sEV) were shown to mediate communication between organs and participate in diabetes progression. Some sEV lncRNAs derived from stem cells are being developed as potential therapeutic agents for diabetic complications. In this review, we summarize the current knowledge relating to lncRNA biogenesis, the mechanisms of lncRNA sorting into sEV and the regulatory roles of lncRNAs and sEV lncRNAs in diabetes. Knowledge of lncRNAs and sEV lncRNAs in diabetes will aid in the development of new therapeutic drugs for T2D in the future.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 11","pages":"526-537"},"PeriodicalIF":4.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/92/TRA-23-526.PMC9828071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9476916","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":"Hox-driven conditional immortalization of myeloid and lymphoid progenitors: Uses, advantages, and future potential.","authors":"Shranjit S Lail,&nbsp;Corey R Arnold,&nbsp;Luiz G N de Almeida,&nbsp;Neil McKenna,&nbsp;Jose A Chiriboga,&nbsp;Antoine Dufour,&nbsp;Amy L Warren,&nbsp;Robin Michael Yates","doi":"10.1111/tra.12869","DOIUrl":"https://doi.org/10.1111/tra.12869","url":null,"abstract":"<p><p>Those who study macrophage biology struggle with the decision whether to utilize primary macrophages derived directly from mice or opt for the convenience and genetic tractability of immortalized macrophage-like cell lines in in vitro studies. Particularly when it comes to studying phagocytosis and phagosomal maturation-a signature cellular process of the macrophage-many commonly used cell lines are not representative of what occurs in primary macrophages. A system developed by Mark Kamps' group, that utilizes conditionally constitutive activity of Hox transcription factors (Hoxb8 and Hoxa9) to immortalize differentiation-competent myeloid cell progenitors of mice, offers an alternative to the macrophage/macrophage-like dichotomy. In this resource, we will review the use of Hoxb8 and Hoxa9 as hematopoietic regulators to conditionally immortalize murine hematopoietic progenitor cells which retain their ability to differentiate into many functional immune cell types including macrophages, neutrophils, basophils, osteoclasts, eosinophils, dendritic cells, as well as limited potential for the generation of lymphocytes. We further demonstrate that the use of macrophages derived from Hoxb8/Hoxa9 immortalized progenitors and their similarities to bone marrow-derived macrophages. To supplement the existing data, mass spectrometry-based proteomics, flow cytometry, cytology, and in vitro phagosomal assays were conducted on macrophages derived from Hoxb8 immortalized progenitors and compared to bone marrow-derived macrophages and the macrophage-like cell line J774. We additionally propose the use of a standardized nomenclature to describe cells derived from the Hoxb8/Hoxa9 system in anticipation of their expanded use in the study of leukocyte cell biology.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 11","pages":"538-553"},"PeriodicalIF":4.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9105905","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}

{"title":"Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis.","authors":"Bethany F Campbell,&nbsp;Brian S Hercyk,&nbsp;Ashlei R Williams,&nbsp;Ema San Miguel,&nbsp;Haylee G Young,&nbsp;Maitreyi E Das","doi":"10.1111/tra.12864","DOIUrl":"https://doi.org/10.1111/tra.12864","url":null,"abstract":"<p><p>Fission yeast cytokinesis is driven by simultaneous septum synthesis, membrane furrowing and actomyosin ring constriction. The septum consists of a primary septum flanked by secondary septa. First, delivery of the glucan synthase Bgs1 and membrane vesicles initiate primary septum synthesis and furrowing. Next, Bgs4 is delivered for secondary septum formation. It is unclear how septum synthesis is coordinated with membrane furrowing. Cdc42 promotes delivery of Bgs1 but not Bgs4. We find that after primary septum initiation, Cdc42 inactivators Rga4 and Rga6 localize to the division site. In rga4Δrga6Δ mutants, Cdc42 activity is enhanced during late cytokinesis and cells take longer to separate. Electron micrographs of the division site in these mutants exhibit malformed septum with irregular membrane structures. These mutants have a larger division plane with enhanced Bgs1 delivery but fail to enhance accumulation of Bgs4 and several exocytic proteins. Additionally, these mutants show endocytic defects at the division site. This suggests that Cdc42 regulates primary septum formation and only certain membrane trafficking events. As cytokinesis progresses Rga4 and Rga6 localize to the division site to decrease Cdc42 activity to allow coupling of Cdc42-independent membrane trafficking events with septum formation for proper septum morphology.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 10","pages":"478-495"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10437282","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}

{"title":"Dynamics of axonal β-actin mRNA in live hippocampal neurons.","authors":"Byung Hun Lee,&nbsp;Seokyoung Bang,&nbsp;Seung-Ryeol Lee,&nbsp;Noo Li Jeon,&nbsp;Hye Yoon Park","doi":"10.1111/tra.12865","DOIUrl":"https://doi.org/10.1111/tra.12865","url":null,"abstract":"<p><p>Localization of mRNA facilitates spatiotemporally controlled protein expression in neurons. In axons, mRNA transport followed by local protein synthesis plays a critical role in axonal growth and guidance. However, it is not yet clearly understood how mRNA is transported to axonal subcellular sites and what regulates axonal mRNA localization. Using a transgenic mouse model in which endogenous β-actin mRNA is fluorescently labeled, we investigated β-actin mRNA movement in axons of hippocampal neurons. We cultured neurons in microfluidic devices to separate axons from dendrites and performed single-particle tracking of axonal β-actin mRNA. Compared with dendritic β-actin mRNA, axonal β-actin mRNA showed less directed motion and exhibited mostly subdiffusive motion, especially near filopodia and boutons in mature dissociated hippocampal neurons. We found that axonal β-actin mRNA was likely to colocalize with actin patches (APs), regions that have a high density of filamentous actin (F-actin) and are known to have a role in branch initiation. Moreover, simultaneous imaging of F-actin and axonal β-actin mRNA in live neurons revealed that moving β-actin mRNA tended to be docked in the APs. Our findings reveal that axonal β-actin mRNA localization is facilitated by actin networks and suggest that localized β-actin mRNA plays a potential role in axon branch formation.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 10","pages":"496-505"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10464797","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":"Correction to: Evolution of factors shaping the endoplasmic reticulum.","authors":"Aspasia Kontou,&nbsp;Emily K Herman,&nbsp;Mark C Field,&nbsp;Joel B Dacks,&nbsp;V Lila Koumandou","doi":"10.1111/tra.12867","DOIUrl":"https://doi.org/10.1111/tra.12867","url":null,"abstract":"Correction to: Evolution of factors shaping the endoplasmic reticulum Aspasia Kontou | Emily K. Herman | Mark C. Field | Joel B. Dacks | V. Lila Koumandou Genetics Laboratory, Department of Biotechnology, Agricultural University of Athens, Athens, Greece Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada School of Life Sciences, University of Dundee, Dundee, UK Biology Centre, Czech Academy of Sciences, České Budějovice, Czech Republic Centre for Life's Origin and Evolution, Department of Genetics, Evolution and Environment, University College of London, London, UK","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 10","pages":"521"},"PeriodicalIF":4.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117599/pdf/TRA-23-521.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9333468","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":"Evolution of factors shaping the endoplasmic reticulum.","authors":"Aspasia Kontou,&nbsp;Emily K Herman,&nbsp;Mark C Field,&nbsp;Joel B Dacks,&nbsp;V Lila Koumandou","doi":"10.1111/tra.12863","DOIUrl":"https://doi.org/10.1111/tra.12863","url":null,"abstract":"<p><p>Endomembrane system compartments are significant elements in virtually all eukaryotic cells, supporting functions including protein synthesis, post-translational modifications and protein/lipid targeting. In terms of membrane area the endoplasmic reticulum (ER) is the largest intracellular organelle, but the origins of proteins defining the organelle and the nature of lineage-specific modifications remain poorly studied. To understand the evolution of factors mediating ER morphology and function we report a comparative genomics analysis of experimentally characterized ER-associated proteins involved in maintaining ER structure. We find that reticulons, REEPs, atlastins, Ufe1p, Use1p, Dsl1p, TBC1D20, Yip3p and VAPs are highly conserved, suggesting an origin at least as early as the last eukaryotic common ancestor (LECA), although many of these proteins possess additional non-ER functions in modern eukaryotes. Secondary losses are common in individual species and in certain lineages, for example lunapark is missing from the Stramenopiles and the Alveolata. Lineage-specific innovations include protrudin, Caspr1, Arl6IP1, p180, NogoR, kinectin and CLIMP-63, which are restricted to the Opisthokonta. Hence, much of the machinery required to build and maintain the ER predates the LECA, but alternative strategies for the maintenance and elaboration of ER shape and function are present in modern eukaryotes. Moreover, experimental investigations for ER maintenance factors in diverse eukaryotes are expected to uncover novel mechanisms.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"23 9","pages":"462-473"},"PeriodicalIF":4.5,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10496488","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":"α‐Synuclein fibrils explore actin‐mediated macropinocytosis for cellular entry into model neuroblastoma neurons","authors":"Pravin Hivare, Joshna Gadhavi, D. Bhatia, Sharad Gupta","doi":"10.1111/tra.12859","DOIUrl":"https://doi.org/10.1111/tra.12859","url":null,"abstract":"Alpha‐synuclein (α‐Syn), an intrinsically disordered protein (IDP), is associated with neurodegenerative disorders, including Parkinson's disease (PD or other α‐synucleinopathies. Recent investigations propose the transmission of α‐Syn protein fibrils, in a prion‐like manner, by entering proximal cells to seed further fibrillization in PD. Despite the recent advances, the mechanisms by which extracellular protein aggregates internalize into the cells remain poorly understood. Using a simple cell‐based model of human neuroblastoma‐derived differentiated neurons, we present the cellular internalization of α‐Syn PFF to check cellular uptake and recycling kinetics along with the standard endocytic markers Transferrin (Tf) marking clathrin‐mediated endocytosis (CME) and Galectin3 (Gal3) marking clathrin‐independent endocytosis (CIE). Specific inhibition of endocytic pathways using chemical inhibitors reveals no significant involvement of CME, CIE and caveolae‐mediated endocytosis (CvME). A substantial reduction in cellular uptake was observed after perturbation of actin polymerization and treatment with macropinosomes inhibitor. Our results show that α‐Syn PFF mainly internalizes into the SH‐SY5Y cells and differentiated neurons via the macropinocytosis pathway. The elucidation of the molecular and cellular mechanism involved in the α‐Syn PFF internalization will help improve the understanding of α‐synucleinopathies including PD, and further design specific inhibitors for the same.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"1 1","pages":"391 - 410"},"PeriodicalIF":4.5,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89127590","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}

{"title":"Myosin V facilitates polarised E‐cadherin secretion","authors":"Dajana Tanasic, N. Berns, V. Riechmann","doi":"10.1111/tra.12846","DOIUrl":"https://doi.org/10.1111/tra.12846","url":null,"abstract":"E‐cadherin has a fundamental role in epithelial tissues by providing cell–cell adhesion. Polarised E‐cadherin exocytosis to the lateral plasma membrane is central for cell polarity and epithelial homeostasis. Loss of E‐cadherin secretion compromises tissue integrity and is a prerequisite for metastasis. Despite this pivotal role of E‐cadherin secretion, the transport mechanism is still unknown. Here we identify Myosin V as the motor for E‐cadherin secretion. Our data reveal that Myosin V and F‐actin are required for the formation of a continuous apicolateral E‐cadherin belt, the zonula adherens. We show by live imaging how Myosin V transports E‐cadherin vesicles to the plasma membrane, and distinguish two distinct transport tracks: an apical actin network leading to the zonula adherens and parallel actin bundles leading to the basal‐most region of the lateral membrane. E‐cadherin secretion starts in endosomes, where Rab11 and Sec15 recruit Myosin V for transport to the zonula adherens. We also shed light on the endosomal sorting of E‐cadherin by showing how Rab7 and Snx16 cooperate in moving E‐cadherin into the Rab11 compartment. Thus, our data help to understand how polarised E‐cadherin secretion maintains epithelial architecture and prevents metastasis.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"73 1","pages":"374 - 390"},"PeriodicalIF":4.5,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90245460","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}