IF 4.5 3区生物学

Traffic Pub Date : 2023-09-01 DOI: 10.1111/tra.12904

Simei Go, Hang Lam Li, Jung-Chin Chang, Arthur J Verhoeven, Ronald P J Oude Elferink

{"title":"Cholangiocytes express an isoform of soluble adenylyl cyclase that is N-linked glycosylated and secreted in extracellular vesicles.","authors":"Simei Go, Hang Lam Li, Jung-Chin Chang, Arthur J Verhoeven, Ronald P J Oude Elferink","doi":"10.1111/tra.12904","DOIUrl":"https://doi.org/10.1111/tra.12904","url":null,"abstract":"Soluble adenylyl cyclase (sAC)-derived cAMP regulates various cellular processes; however, the regulatory landscape mediating sAC protein levels remains underexplored. We consistently observed a 85 kD (sAC85 ) or 75 kD (sAC75 ) sAC protein band under glucose-sufficient or glucose-deprived states, respectively, in H69 cholangiocytes by immunoblotting. Deglycosylation by PNGase-F demonstrated that both sAC75 and sAC85 are N-linked glycosylated proteins with the same polypeptide backbone. Deglycosylation with Endo-H further revealed that sAC75 and sAC85 carry distinct sugar chains. We observed release of N-linked glycosylated sAC (sACEV ) in extracellular vesicles under conditions that support intracellular sAC85 (glucose-sufficient) as opposed to sAC75 (glucose-deprived) conditions. Consistently, disrupting the vesicular machinery affects the maturation of intracellular sAC and inhibits the release of sACEV into extracellular vesicles. The intracellular turnover of sAC85 is extremely short (t1/2 ~30 min) and release of sACEV in the medium was detected within 3 h. Our observations support the maturation and trafficking in cholangiocytes of an N-linked glycosylated sAC isoform that is rapidly released into extracellular vesicles.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 9","pages":"413-430"},"PeriodicalIF":4.5,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9944282","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: 2

Deacidification of endolysosomes by neuronal aging drives synapse loss. 神经元老化导致内溶酶体脱酸，导致突触丢失。

IF 4.5 3区生物学

Traffic Pub Date : 2023-08-01 DOI: 10.1111/tra.12889

Tatiana Burrinha, César Cunha, Michael J Hall, Mafalda Lopes-da-Silva, Miguel C Seabra, Cláudia Guimas Almeida

{"title":"Deacidification of endolysosomes by neuronal aging drives synapse loss.","authors":"Tatiana Burrinha, César Cunha, Michael J Hall, Mafalda Lopes-da-Silva, Miguel C Seabra, Cláudia Guimas Almeida","doi":"10.1111/tra.12889","DOIUrl":"https://doi.org/10.1111/tra.12889","url":null,"abstract":"Previously, we found that age-dependent accumulation of beta-amyloid is not sufficient to cause synaptic decline. Late-endocytic organelles (LEOs) may be driving synaptic decline as lysosomes (Lys) are a target of cellular aging and relevant for synapses. We found that LAMP1-positive LEOs increased in size and number and accumulated near synapses in aged neurons and brains. LEOs' distal accumulation might relate to the increased anterograde movement in aged neurons. Dissecting the LEOs, we found that late-endosomes accumulated while there are fewer terminal Lys in aged neurites, but not in the cell body. The most abundant LEOs were degradative Lys or endolysosomes (ELys), especially in neurites. ELys activity was reduced because of acidification defects, supported by the reduction in v-ATPase subunit V0a1 with aging. Increasing the acidification of aged ELys recovered degradation and reverted synaptic decline, while alkalinization or v-ATPase inhibition, mimicked age-dependent Lys and synapse dysfunction. We identify ELys deacidification as a neuronal mechanism of age-dependent synapse loss. Our findings suggest that future therapeutic strategies to address endolysosomal defects might be able to delay age-related synaptic decline.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 8","pages":"334-354"},"PeriodicalIF":4.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10126393","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: 2

Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models. 哺乳动物内质网相关蛋白降解的遗传破坏:人类表型和动物及细胞疾病模型。

IF 4.5 3区生物学

Traffic Pub Date : 2023-08-01 DOI: 10.1111/tra.12902

Sally Badawi, Feda E Mohamed, Divya Saro Varghese, Bassam R Ali

引用次数: 0

Syntaxin-5's flexibility in SNARE pairing supports Golgi functions. Syntaxin-5 在 SNARE 配对中的灵活性支持高尔基体的功能。

IF 3.6 3区生物学

Traffic Pub Date : 2023-08-01 Epub Date: 2023-06-21 DOI: 10.1111/tra.12903

Zinia D'Souza, Irina Pokrovskaya, Vladimir V Lupashin

{"title":"Syntaxin-5's flexibility in SNARE pairing supports Golgi functions.","authors":"Zinia D'Souza, Irina Pokrovskaya, Vladimir V Lupashin","doi":"10.1111/tra.12903","DOIUrl":"10.1111/tra.12903","url":null,"abstract":"Deficiency in the conserved oligomeric Golgi (COG) complex that orchestrates SNARE-mediated tethering/fusion of vesicles that recycle the Golgi's glycosylation machinery results in severe glycosylation defects. Although two major Golgi v-SNAREs, GS28/GOSR1, and GS15/BET1L, are depleted in COG-deficient cells, the complete knockout of GS28 and GS15 only modestly affects Golgi glycosylation, indicating the existence of an adaptation mechanism in Golgi SNARE. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed two novel Golgi SNARE complexes-STX5/SNAP29/VAMP7 and STX5/VTI1B/STX8/YKT6. These complexes are present in wild-type cells, but their usage is significantly increased in both GS28- and COG-deficient cells. Upon GS28 deletion, SNAP29 increased its Golgi residency in a STX5-dependent manner. While STX5 depletion and Retro2-induced diversion from the Golgi severely affect protein glycosylation, GS28/SNAP29 and GS28/VTI1B double knockouts alter glycosylation similarly to GS28 KO, indicating that a single STX5-based SNARE complex is sufficient to support Golgi glycosylation. Importantly, co-depletion of three Golgi SNARE complexes in GS28/SNAP29/VTI1B TKO cells resulted in severe glycosylation defects and a reduced capacity for glycosylation enzyme retention at the Golgi. This study demonstrates the remarkable plasticity in SXT5-mediated membrane trafficking, uncovering a novel adaptive response to the failure of canonical intra-Golgi vesicle tethering/fusion machinery.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 8","pages":"355-379"},"PeriodicalIF":3.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769259","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

Pseudophosphatase STYXL1 depletion enhances glucocerebrosidase trafficking to lysosomes via ER stress. 假磷酸酶 STYXL1 的耗竭可通过 ER 压力增强葡萄糖脑苷脂向溶酶体的贩运。

IF 4.5 3区生物学

Traffic Pub Date : 2023-07-01 Epub Date: 2023-05-17 DOI: 10.1111/tra.12886

Saloni Patel, Anshul Milap Bhatt, Priyanka Bhansali, Subba Rao Gangi Setty

{"title":"Pseudophosphatase STYXL1 depletion enhances glucocerebrosidase trafficking to lysosomes via ER stress.","authors":"Saloni Patel, Anshul Milap Bhatt, Priyanka Bhansali, Subba Rao Gangi Setty","doi":"10.1111/tra.12886","DOIUrl":"10.1111/tra.12886","url":null,"abstract":"Pseudophosphatases are catalytically inactive but share sequence and structural similarities with classical phosphatases. STYXL1 is a pseudophosphatase that belongs to the family of dual-specificity phosphatases and is known to regulate stress granule formation, neurite formation and apoptosis in different cell types. However, the role of STYXL1 in regulating cellular trafficking or the lysosome function has not been elucidated. Here, we show that the knockdown of STYXL1 enhances the trafficking of β-glucocerebrosidase (β-GC) and its lysosomal activity in HeLa cells. Importantly, the STYXL1-depleted cells display enhanced distribution of endoplasmic reticulum (ER), late endosome and lysosome compartments. Further, knockdown of STYXL1 causes the nuclear translocation of unfolded protein response (UPR) and lysosomal biogenesis transcription factors. However, the upregulated β-GC activity in the lysosomes is independent of TFEB/TFE3 nuclear localization in STYXL1 knockdown cells. The treatment of STYXL1 knockdown cells with 4-PBA (ER stress attenuator) significantly reduces the β-GC activity equivalent to control cells but not additive with thapsigargin, an ER stress activator. Additionally, STYXL1-depleted cells show the enhanced contact of lysosomes with ER, possibly via increased UPR. The depletion of STYXL1 in human primary fibroblasts derived from Gaucher patients showed moderately enhanced lysosomal enzyme activity. Overall, these studies illustrated the unique role of pseudophosphatase STYXL1 in modulating the lysosome function both in normal and lysosome-storage disorder cell types. Thus, designing small molecules against STYXL1 possibly can restore the lysosome activity by enhancing ER stress in Gaucher disease.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 7","pages":"254-269"},"PeriodicalIF":4.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9622093","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

Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages. 氧化胆固醇酯可诱导脂质巨噬细胞中功能失调溶酶体的外泌。

IF 4.5 3区生物学

Traffic Pub Date : 2023-07-01 Epub Date: 2023-05-02 DOI: 10.1111/tra.12888

Neuza Domingues, André R A Marques, Rita Diogo Almeida Calado, Inês S Ferreira, Cristiano Ramos, José Ramalho, Maria I L Soares, Telmo Pereira, Luís Oliveira, José R Vicente, Louise H Wong, Inês C M Simões, Teresa M V D Pinho E Melo, Andrew Peden, Cláudia Guimas Almeida, Clare E Futter, Rosa Puertollano, Winchil L C Vaz, Otília V Vieira

{"title":"Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages.","authors":"Neuza Domingues, André R A Marques, Rita Diogo Almeida Calado, Inês S Ferreira, Cristiano Ramos, José Ramalho, Maria I L Soares, Telmo Pereira, Luís Oliveira, José R Vicente, Louise H Wong, Inês C M Simões, Teresa M V D Pinho E Melo, Andrew Peden, Cláudia Guimas Almeida, Clare E Futter, Rosa Puertollano, Winchil L C Vaz, Otília V Vieira","doi":"10.1111/tra.12888","DOIUrl":"10.1111/tra.12888","url":null,"abstract":"A key event in atherogenesis is the formation of lipid-loaded macrophages, lipidotic cells, which exhibit irreversible accumulation of undigested modified low-density lipoproteins (LDL) in lysosomes. This event culminates in the loss of cell homeostasis, inflammation, and cell death. Nevertheless, the exact chemical etiology of atherogenesis and the molecular and cellular mechanisms responsible for the impairment of lysosome function in plaque macrophages are still unknown. Here, we demonstrate that macrophages exposed to cholesteryl hemiazelate (ChA), one of the most prevalent products of LDL-derived cholesteryl ester oxidation, exhibit enlarged peripheral dysfunctional lysosomes full of undigested ChA and neutral lipids. Both lysosome area and accumulation of neutral lipids are partially irreversible. Interestingly, the dysfunctional peripheral lysosomes are more prone to fuse with the plasma membrane, secreting their undigested luminal content into the extracellular milieu with potential consequences for the pathology. We further demonstrate that this phenotype is mechanistically linked to the nuclear translocation of the MiT/TFE family of transcription factors. The induction of lysosome biogenesis by ChA appears to partially protect macrophages from lipid-induced cytotoxicity. In sum, our data show that ChA is involved in the etiology of lysosome dysfunction and promotes the exocytosis of these organelles. This latter event is a new mechanism that may be important in the pathogenesis of atherosclerosis.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 7","pages":"284-307"},"PeriodicalIF":4.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978553","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

Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole. Syntaxin 3 SPI-2 依赖性串联促进了含有液泡的沙门氏菌的分裂。

IF 4.5 3区生物学

Traffic Pub Date : 2023-07-01 Epub Date: 2023-04-28 DOI: 10.1111/tra.12887

Ritika Chatterjee, Abhilash Vijay Nair, Anmol Singh, Nishi Mehta, Subba Rao Gangi Setty, Dipshikha Chakravortty

{"title":"Syntaxin 3 SPI-2 dependent crosstalk facilitates the division of Salmonella containing vacuole.","authors":"Ritika Chatterjee, Abhilash Vijay Nair, Anmol Singh, Nishi Mehta, Subba Rao Gangi Setty, Dipshikha Chakravortty","doi":"10.1111/tra.12887","DOIUrl":"10.1111/tra.12887","url":null,"abstract":"Intracellular membrane fusion is mediated by membrane-bridging complexes of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). SNARE proteins are one of the key players in vesicular transport. Several reports shed light on intracellular bacteria modulating host SNARE machinery to establish infection successfully. The critical SNAREs in macrophages responsible for phagosome maturation are Syntaxin 3 (STX3) and Syntaxin 4 (STX4). Reports also suggest that Salmonella actively modulates its vacuole membrane composition to escape lysosomal fusion. Salmonella containing vacuole (SCV) harbours recycling endosomal SNARE Syntaxin 12 (STX12). However, the role of host SNAREs in SCV biogenesis and pathogenesis remains unclear. Upon knockdown of STX3, we observed a reduction in bacterial proliferation, which is concomitantly restored upon the overexpression of STX3. Live-cell imaging of Salmonella-infected cells showed that STX3 localises to the SCV membranes and thus might help in the fusion of SCV with intracellular vesicles to acquire membrane for its division. We also found the interaction STX3-SCV was abrogated when we infected with SPI-2 encoded Type 3 secretion system (T3SS) apparatus mutant (STM ∆ssaV) but not with SPI-1 encoded T3SS apparatus mutant (STM ∆invC). These observations were also consistent in the mice model of Salmonella infection. Together, these results shed light on the effector molecules secreted through T3SS encoded by SPI-2, possibly involved in interaction with host SNARE STX3, which is essential to maintain the division of Salmonella in SCV and help to maintain a single bacterium per vacuole.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 7","pages":"270-283"},"PeriodicalIF":4.5,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9664687","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

Out of the ESCPE room: Emerging roles of endosomal SNX-BARs in receptor transport and host-pathogen interaction. 走出 ESCPE 会议室：内体 SNX-BAR 在受体转运和宿主与病原体相互作用中的新作用。

IF 4.5 3区生物学

Traffic Pub Date : 2023-06-01 Epub Date: 2023-04-23 DOI: 10.1111/tra.12885

Boris Simonetti, James L Daly, Peter J Cullen

{"title":"Out of the ESCPE room: Emerging roles of endosomal SNX-BARs in receptor transport and host-pathogen interaction.","authors":"Boris Simonetti, James L Daly, Peter J Cullen","doi":"10.1111/tra.12885","DOIUrl":"10.1111/tra.12885","url":null,"abstract":"Several functions of the human cell, such as sensing nutrients, cell movement and interaction with the surrounding environment, depend on a myriad of transmembrane proteins and their associated proteins and lipids (collectively termed \"cargoes\"). To successfully perform their tasks, cargo must be sorted and delivered to the right place, at the right time, and in the right amount. To achieve this, eukaryotic cells have evolved a highly organized sorting platform, the endosomal network. Here, a variety of specialized multiprotein complexes sort cargo into itineraries leading to either their degradation or their recycling to various organelles for further rounds of reuse. A key sorting complex is the Endosomal SNX-BAR Sorting Complex for Promoting Exit (ESCPE-1) that promotes the recycling of an array of cargos to the plasma membrane and/or the trans-Golgi network. ESCPE-1 recognizes a hydrophobic-based sorting motif in numerous cargoes and orchestrates their packaging into tubular carriers that pinch off from the endosome and travel to the target organelle. A wide range of pathogens mimic this sorting motif to hijack ESCPE-1 transport to promote their invasion and survival within infected cells. In other instances, ESCPE-1 exerts restrictive functions against pathogens by limiting their replication and infection. In this review, we discuss ESCPE-1 assembly and functions, with a particular focus on recent advances in the understanding of its role in membrane trafficking, cellular homeostasis and host-pathogen interaction.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 6","pages":"234-250"},"PeriodicalIF":4.5,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9685389","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

SWIP mediates retromer-independent membrane recruitment of the WASH complex. SWIP介导WASH复合物的逆转录酶非依赖性膜募集。

IF 4.5 3区生物学

Traffic Pub Date : 2023-05-01 Epub Date: 2023-03-30 DOI: 10.1111/tra.12884

Vojtěch Dostál, Tereza Humhalová, Pavla Beránková, Ondřej Pácalt, Lenka Libusová

引用次数: 2

Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal-lysosomal system in the ARPE-19 retinal pigment epithelial cell line. 半胱氨酸白三烯受体1是ARPE-19视网膜色素上皮细胞系内溶酶体系统的有效调节剂。

IF 4.5 3区生物学

Traffic Pub Date : 2023-04-01 DOI: 10.1111/tra.12881

Andreas Koller, Susanne Maria Brunner, Julia Preishuber-Pflügl, Christian Runge, Anja-Maria Ladek, Herbert Anton Reitsamer, Andrea Trost

{"title":"Cysteinyl leukotriene receptor 1 is a potent regulator of the endosomal-lysosomal system in the ARPE-19 retinal pigment epithelial cell line.","authors":"Andreas Koller, Susanne Maria Brunner, Julia Preishuber-Pflügl, Christian Runge, Anja-Maria Ladek, Herbert Anton Reitsamer, Andrea Trost","doi":"10.1111/tra.12881","DOIUrl":"https://doi.org/10.1111/tra.12881","url":null,"abstract":"The endosomal-lysosomal system is central for cell homeostasis and comprises the functions and dynamics of particular organelles including endosomes, lysosomes and autophagosomes. In previous studies, we found that the cysteinyl leukotriene receptor 1 (CysLTR1) regulates autophagy in the retinal pigment epithelial cell line ARPE-19 under basal cellular conditions. However, the underlying mechanism by which CysLTR1 regulates autophagy is unknown. Thus, in the present study, the effects of CysLTR1 inhibition on the endosomal-lysosomal system are analyzed in detail to identify the role of CysLTR1 in cell homeostasis and autophagy regulation. CysLTR1 inhibition in ARPE-19 cells by Zafirlukast, a CysLTR1 antagonist, depleted the lysosomal pool. Furthermore, CysLTR1 antagonization reduced endocytic capacity and internalization of epidermal growth factor and decreased levels of the transferrin receptor, CD71. Serum starvation abolished the effect of Zafirlukast on the autophagic flux, which identifies the endocytic regulation of serum components by CysLTR1 as an important autophagy-modulating mechanism. The role of CysLTR1 in inflammation and cell stress has been exceedingly studied, but its involvement in the endosomal-lysosomal pathway is largely unknown. This current study provides new insights into basal activity of CysLTR1 on cellular endocytosis and the subsequent impact on downstream processes like autophagy.","PeriodicalId":23207,"journal":{"name":"Traffic","volume":"24 4","pages":"177-189"},"PeriodicalIF":4.5,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9550154","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: 2

Traffic最新文献