Traffic最新文献

{"title":"From Mechanisms to Therapy: Exploring the Role of Ferroptosis in Cervical Cancer Transformation and Treatment.","authors":"Zhenlei Wang, Yuanyuan Xiao, Ranzhong Chen, Erqun Tang, Shuangyang Tang","doi":"10.1111/tra.70018","DOIUrl":"https://doi.org/10.1111/tra.70018","url":null,"abstract":"<p><p>Cervical cancer (CC) exerts a considerable impact on women's health worldwide and presents persistent challenges to conventional therapeutic strategies due to its propensity for distant metastasis, postoperative recurrence, and variable drug resistance. Ferroptosis, a recently identified type of programmed cell death, offers promising potential for a therapeutic approach for CC. This paper reviews the regulatory processes involved in ferroptosis, including the sequential events leading to cell membrane rupture via lipid peroxidation and the changes in ferroptosis sensitivity as cervical cells progress from a healthy to a malignant condition. Additionally, the dynamic relationship between ferroptosis and CC transformation driven by high-risk HPV (HR-HPV) infection is examined, with a particular focus on how HR-HPV E6/E7 proteins influence ferroptosis sensitivity. By examining the factors associated with ferroptosis, this review provides insights into CC progression and prognosis. Furthermore, therapeutic strategies targeting ferroptosis are discussed, offering novel perspectives for effective treatment options for CC.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70018"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970386","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":"Eukaryote-Wide Distribution of a Family of Longin Domain-Containing GAP Complexes for Small GTPases.","authors":"Anna M G Novák Vanclová, Catherine L Jackson, Joel B Dacks","doi":"10.1111/tra.70016","DOIUrl":"10.1111/tra.70016","url":null,"abstract":"<p><p>Arf and Rab family small GTPases and their regulators, GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), play a central role in membrane trafficking. In this study, we focused on a recently reported GAP for Arf (and potentially Rab) proteins, the CSW complex, a part of a small family of longin domain-containing proteins that form complexes with GAP activity. This family also includes folliculin and GATOR1, which are GAPs for the Rag/Gtr GTPases. All three complexes are associated with lysosomes and play a role in nutrient signaling, the latter two being directly involved in the mTOR pathway. The role of CSW is not clear, but in addition to having GAP activity on Arf proteins in vitro, its mutation causes severe neurodegenerative diseases. Here we update the reported pan-eukaryotic presence of folliculin and GATOR1, and demonstrate that CSW is also found throughout eukaryotes, though with sporadic distribution. We identify highly conserved motifs in all CSW subunits, some shared with the catalytic subunits of folliculin and GATOR1, that provide new potential avenues for experimental exploration. Remarkably, one such conserved sequence, the \"GP\" motif, is also found in structurally related longin proteins present in the archaeal ancestor of eukaryotes.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70016"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708959","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":"CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1.","authors":"Gunjan Misri, Ajay B Murakonda, Naava Naslavsky, Steve Caplan","doi":"10.1111/tra.70015","DOIUrl":"10.1111/tra.70015","url":null,"abstract":"<p><p>Recycling endosomes are essential for membrane trafficking, retrieving internalized cell surface receptors and lipids to the plasma membrane. In this study, we investigate the dynamics of tubular recycling endosomes (TREs) and their regulation. We demonstrate that TREs are highly dynamic structures that first undergo biogenesis and later fission upon internalization of CD98, a known clathrin-independent cargo. Our findings identify two new constituents and novel regulators of TRE function, CD2AP and CIN85, which are recruited to TRE through interactions with MICAL-L1 via their SH3 domains. Depletion of either CD2AP or CIN85 impairs recycling, demonstrating that these proteins play important roles in TRE function. Our study highlights the importance of coordinated protein interactions in maintaining endosomal function and identifies CD2AP and CIN85 as key regulators of the recycling pathway, potentially through their impact on the actin cytoskeleton. Understanding these mechanisms provides new insights into membrane trafficking and may have implications for diseases where endosomal recycling is disrupted.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70015"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754386","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":"Spatiotemporal Analysis of Glucagon Secretory Granule Dynamics.","authors":"Samuele Ghignoli, Valentina De Lorenzi, Gianmarco Ferri, Licia Anna Pugliese, Marta Tesi, Piero Marchetti, Stefano Luin, Francesco Cardarelli","doi":"10.1111/tra.70019","DOIUrl":"10.1111/tra.70019","url":null,"abstract":"<p><p>The secretion of insulin and glucagon by pancreatic β and α cells, respectively, is critical for glucose homeostasis. While the insulin granule dynamics are well-characterized, the intracellular behavior of glucagon secretory granules (GSG) remains poorly understood. Here, we analyze the mobility of GSGs in αTC1-9 cells and insulin secretory granules (ISG) in INS-1E cells using spatiotemporal correlation spectroscopy and single-particle tracking (SPT), with a focus on the role of the cytoskeleton in regulating their transport. Under basal conditions, SPT classification reveals that GSGs predominantly exhibit diffusive motion (57.6% ± 10%), with smaller fractions categorized as almost immobile (35.8% ± 10.6%) or drifted (6.6% ± 3%), closely resembling ISG dynamics. By disrupting microtubules, we confirmed their role as active tracks for directed granule transport in both cell types. Upon exposure to their respective secretory stimuli-high glucose for β cells and low glucose for α cells-both granule populations underwent a comparable shift toward increased diffusive and drifted motions. Treatment with the actin depolymerizing agent Latrunculin-B reproduced this stimulatory effect in INS-1E cells but not in αTC1-9 cells, suggesting that despite their overall similarity in granule behavior under physiological conditions, α and β cells may rely on partially distinct mechanisms to engage the cytoskeletal network.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70019"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132038","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":"FGF Signaling Promotes Lysosome Biogenesis in Chondrocytes via the Mannose Phosphate Receptor Pathway.","authors":"Laura Cinque, Maria Iavazzo, Gennaro Di Bonito, Elena Polishchuk, Rossella De Cegli, Carmine Settembre","doi":"10.1111/tra.70013","DOIUrl":"10.1111/tra.70013","url":null,"abstract":"<p><p>The mannose 6-phosphate (M6P) pathway is critical for lysosome biogenesis, facilitating the trafficking of hydrolases to lysosomes to ensure cellular degradative capacity. Fibroblast Growth Factor (FGF) signaling, a key regulator of skeletogenesis, has been linked to the autophagy-lysosomal pathway in chondrocytes, but its role in lysosome biogenesis remains poorly characterized. Here, using mass spectrometry, lysosome immune-purification, and functional assays, we reveal that RCS (Swarm rat chondrosarcoma cells) lacking FGF receptors 3 and 4 exhibit dysregulations of the M6P pathway, resulting in hypersecretion of lysosomal enzymes and impaired lysosomal function. We found that FGF receptors control the expression of M6P receptor genes in response to FGF stimulation and during cell cycle via the activation of the transcription factors TFEB and TFE3. Notably, restoring M6P pathway-either through gene expression or activation of TFEB-significantly rescues lysosomal defects in FGFR3;4-deficient RCS. These findings uncover a novel mechanism by which FGF signaling regulates lysosomal function, offering insights into the control of chondrocyte catabolism and the understanding of FGF-related human diseases.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70013"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144761432","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":"Strain-Dependent Immune Signaling by Small Extracellular Vesicles Derived From Trypanosoma cruzi-Infected Macrophages.","authors":"Andrea C Mesías, María Elisa Vázquez, Maximiliano Cosenza, Sandra N Poulakidas, Federico Ramos, Leonardo Acuña, Cecilia Pérez Brandán, Valeria Tekiel, Cecilia Parodi","doi":"10.1111/tra.70017","DOIUrl":"https://doi.org/10.1111/tra.70017","url":null,"abstract":"<p><p>Among extracellular vesicles (EVs), exosomes, comprised within small EVs are bilayered nanovesicles carrying specific cargo that are released into the interstitial space in a highly regulated manner. In this study, we investigated the message transmitted through macrophage-derived small EVs in response to the interaction with Trypanosoma cruzi, the protozoan responsible for Chagas disease. We utilized two distinct parasite strains, the virulent CL Brener and the attenuated TCC. When taken up by naϊve macrophages (Mφs) in vitro, small EVs derived from TCC-infected cells favor an adverse environment for parasite spread, with M1-like cytokine pattern. In contrast, EVs from CL Brener-infected cells fostered a more permissive environment with reduced TNF-α/IL-10 ratio, higher phagocytic activity and reduced migration capacity, which may hinder a timely immune response. Further, while naïve Mφs' EVs induced iNOS and nitric oxide (NO) secretion, EVs from T. cruzi-infected Mφs failed to robustly activate iNOS, suggesting the parasite may modulate EV-mediated communication to avoid NO toxicity. In vivo assays showed distinct parasitemia courses with higher parasite burden when mice were treated with small EVs from CL Brener-infected Mφs. Overall, small EVs released by infected Mφs serve as messengers in T. cruzi infection, inducing different immune responses based on parasite virulence.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 7-9","pages":"e70017"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970389","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":"TENT5/FAM46: An Enigmatic Family of Secretory Tuners.","authors":"Daniel Lacidogna, Sara Pennacchio, Enrico Milan","doi":"10.1111/tra.70011","DOIUrl":"10.1111/tra.70011","url":null,"abstract":"<p><p>Human TENT5 family comprises four members (A-D) associated with different diseases of secretory cells. Homozygous mutations in TENT5A cause a rare form of osteogenesis imperfecta due to impaired collagen deposition by osteoblasts. TENT5C is frequently mutated or deleted in patients with multiple myeloma, the cancer of antibody-secreting plasma cells, and TENT5D alterations result in male infertility. TENT5 members are noncanonical poly(A)polymerases that selectively stabilize mRNAs encoding endoplasmic reticulum-imported proteins, thus promoting the expression of secretory cargoes and proteins involved in folding, glycosylation, and trafficking along the secretory apparatus. This specificity has been proposed to be linked to TENT5 localization at the membrane of the endoplasmic reticulum, thanks to their interaction with transmembrane FNDC3 proteins. Recently, key roles of TENT5 proteins have been described in cancer, bone homeostasis, immunity, stemness, and fertility. This review will comprehensively analyze the identified cellular functions of this novel family of secretory tuners in physiological and pathological conditions, highlighting the proposed molecular mechanisms and the remaining open questions.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70011"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128663","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":"TNF-α-Driven Changes in Polarized EGF Receptor Trafficking Facilitate Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling From the Apical Surface of MDCK Epithelial Cells.","authors":"Syntyche Ngalula, Cathleen R Carlin","doi":"10.1111/tra.70005","DOIUrl":"https://doi.org/10.1111/tra.70005","url":null,"abstract":"<p><p>This manuscript describes a novel unconventional secretory pathway that facilitates EGF receptor (EGFR) signaling from apical membranes in polarized epithelial cells responding to immune cell mediators. Epithelial tissues provide a physical barrier between our bodies and the external environment and share an intimate relationship with circulating and local immune cells. Our studies describe an unexpected connection between the proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) and EGFR typically localized to basolateral membranes in polarized epithelial cells. These two molecules sit atop complex biological networks with a long history of shared investigative interest from the vantage point of signaling pathway interactions. We have discovered that TNF-α alters the functional landscape of fully polarized epithelial cells by changing the speed and direction of EGFR secretion. Our results show apical EGFR delivery occurs within minutes of de novo synthesis likely via a direct route from the endoplasmic reticulum without passage through the Golgi complex. Additionally, our studies have revealed that apical cellular compartmentalization constitutes an important mechanism to specify EGFR signaling via phosphatidylinositol-4,5-bisphosphate 3-kinase/protein-kinase-B pathways. Our study paves the way for a better understanding of how inflammatory cytokines fine-tune local homeostatic and inflammatory responses by altering the spatial organization of epithelial cell signaling systems.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70005"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050076","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":"A Sensitive and Versatile Cell-Based Assay Combines Luminescence and Trapping Approaches to Monitor Unconventional Protein Secretion.","authors":"Morgane Denus, Aurore Filaquier, William Fargues, Eloïse Néel, Sarah E Stewart, Maëlle Colladant, Thomas Curel, Alexandre Mezghrani, Philippe Marin, Sylvie Claeysen, David C Rubinsztein, Marie-Laure Parmentier, Julien Villeneuve","doi":"10.1111/tra.70009","DOIUrl":"10.1111/tra.70009","url":null,"abstract":"<p><p>In addition to the conventional endoplasmic reticulum (ER)-Golgi secretory pathway, alternative routes are increasingly recognized for their critical roles in exporting a growing number of secreted factors. These alternative processes, collectively referred to as unconventional protein secretion (UcPS), challenge traditional views of protein and membrane trafficking. Unlike the well-characterized molecular machinery of the conventional secretory pathway, the mechanisms underlying UcPS remain poorly understood. Various UcPS pathways may involve direct transport of cytosolic proteins across the plasma membrane or the incorporation of cargo proteins into intracellular compartments redirected for secretion. Identifying the specific chaperones, transporters and fusion machinery involved in UcPS cargo recognition, selection and transport is crucial to decipher how cargo proteins are selectively or synergistically directed through multiple secretory routes. These processes can vary depending on cell type and in response to particular stress conditions or cellular demands, underscoring the need for standardized tools and methods to study UcPS. Here, we combine the sensitivity of split NanoLuc Binary Technology with the versatility of the Retention Using Selective Hooks (RUSH) system to develop a straightforward and reliable cell-based assay for investigating both conventional and unconventional protein secretion. This system allows for the identification of intracellular compartments involved in UcPS cargo trafficking. Additionally, its sensitivity enabled us to demonstrate that disease-associated mutants or variants of Tau and superoxide dismutase-1 (SOD1) show altered secretion via UcPS. Finally, we leveraged this assay to screen for Alzheimer's disease risk factors, revealing a functional link between amyloid-beta production and Tau UcPS. This robust assay provides a powerful tool for increasing our knowledge of protein secretion mechanisms in physiological and pathological contexts.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70009"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111993","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":"BicD and MAP7 Collaborate to Activate Homodimeric Drosophila Kinesin-1 by Complementary Mechanisms.","authors":"M Yusuf Ali, Hailong Lu, Patricia M Fagnant, Jill E Macfarlane, Kathleen M Trybus","doi":"10.1111/tra.70008","DOIUrl":"10.1111/tra.70008","url":null,"abstract":"<p><p>The folded auto-inhibited state of kinesin-1 is stabilized by multiple weak interactions and binds poorly to microtubules. Here we investigate the extent to which homodimeric Drosophila kinesin-1 lacking light chains is activated by the dynein activating adaptor Drosophila BicD. We show that one or two kinesins can bind to the central region of BicD (CC2), a region distinct from that which binds dynein-dynactin (CC1) and cargo-adaptor proteins (CC3). Kinesin light chain significantly reduces the amount of kinesin bound to BicD and thus regulates this interaction. Binding of BicD to kinesin enhances processive motion, suggesting that the adaptor relieves kinesin auto-inhibition. In contrast, the kinesin-binding domain of microtubule-associated protein 7 (MAP7) has minimal impact on the fraction of motors moving processively while full-length MAP7 enhances kinesin-1 recruitment to the microtubule and run length because of its microtubule-binding domain. BicD thus relieves auto-inhibition of kinesin, while MAP7 enhances motor engagement with the microtubules. When BicD and MAP7 are combined, the most robust activation of kinesin-1 occurs, highlighting the crosstalk between adaptors and microtubule-associated proteins in regulating transport.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"26 4-6","pages":"e70008"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094978","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}