Glycoconjugate Journal最新文献

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Substrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase. 发酵支原体mf1磷酸胆碱转移酶的底物柔韧性。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-03-22 DOI: 10.1007/s10719-025-10181-2
Lena Nuschy, Biswajit Sarkar, Alla Zamyatina, Iain B H Wilson
{"title":"Substrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase.","authors":"Lena Nuschy, Biswajit Sarkar, Alla Zamyatina, Iain B H Wilson","doi":"10.1007/s10719-025-10181-2","DOIUrl":"10.1007/s10719-025-10181-2","url":null,"abstract":"<p><p>Zwitterionic modifications of glycans such as phosphorylcholine or phosphoethanolamine occur in a wide range of prokaryotic and eukaryotic organisms and are known for interaction with the mammalian immune system. Unlike the biosynthesis of membrane phospholipids which is well elucidated, very little is known about the transfer of zwitterionic phosphodiester moieties onto glycoconjugates. The presence and function of relevant enzymes has been suggested by gene knockout or mutation and corresponding aberrant phosphorylcholine metabolism. In the current study, the Mycoplasma fermentans phosphorylcholine transferase mf1, with previously confirmed in-vitro activity synthesizing phosphorylcholine-α-glucosyl-1,2-dipalmitoyl glycerol, is demonstrated to not only transfer phosphorylcholine but also phosphoethanolamine from CDP-ethanolamine. Moreover, mf1 is capable of using the β-configuration of the presumed natural substrate but transfers neither to simpler substrates with glucose moieties such as β-D-octyl-glucopyranoside nor to an extended lipid substrate with an additional galactose residue. These findings suggest a certain, but limited, substrate flexibility for bacterial PC-transferases. Mf1 activity is inhibited by β-glycerophosphate, an isomer of part of CDP-glycerol which is known to compete with CDP-ribitol in enzymatic reactions catalyzed by fukutin, a human protein sharing structural homology with mf1. For the first time, a phosphorylcholine transferase, mf1, could be biochemically characterized in vitro and its lipid products with zwitterionic phosphodiesters attached could be detected specifically with the pentraxin serum amyloid P.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"87-96"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Cartilaginous fishes-derived chondroitin sulfates potentially suppress lipid droplet accumulation in the differentiated 3T3-L1 adipocytes. 软骨鱼来源的硫酸软骨素可能抑制分化的3T3-L1脂肪细胞中的脂滴积累。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-03-10 DOI: 10.1007/s10719-025-10183-0
Danang Dwi Cahyadi, Katsuhiko Warita, Naoko Takeda-Okuda, Jun-Ichi Tamura, Yoshinao Z Hosaka
{"title":"Cartilaginous fishes-derived chondroitin sulfates potentially suppress lipid droplet accumulation in the differentiated 3T3-L1 adipocytes.","authors":"Danang Dwi Cahyadi, Katsuhiko Warita, Naoko Takeda-Okuda, Jun-Ichi Tamura, Yoshinao Z Hosaka","doi":"10.1007/s10719-025-10183-0","DOIUrl":"10.1007/s10719-025-10183-0","url":null,"abstract":"<p><p>In this study, we investigated for cell proliferative and adipogenic differentiation inhibitory activities of chondroitin sulfate (CS) from cartilaginous fish: mako shark (Isurus oxyrinchus, spine part, Ms-CS), blue shark (Prionace glauca, spine part, Bs-CS), sharpspine skate (Okamejei acutispina, head and tail parts, Sp-CS) and stingray (Dasyatis akajei, head part, St-CS) on 3T3-L1 cells. Most of the CSs from cartilaginous fish showed concentration-dependent cell proliferative activity of 3T3-L1 cells within the retrieved concentration range (0-1,000 μg/mL), while under induction of adipocyte differentiation, they inhibited lipid accumulation. In particular, Ms-CS and Sp-CS were highly active in inhibiting lipid accumulation in the cells. The present study revealed that cartilaginous fish-derived CS has inhibitory activity on 3T3-L1 adipocyte differentiation by suppressing lipid droplet accumulation, although the degree of suppression varied depending on the composition of the CS and its origin. In addition, a significant increase in chondroitin sulfate N-acetylgalactosaminyltransferase 2 (Csgalnact2) expression of the Sp-CS group at the concentration of 500 µg/mL was observed. Csgalnact2 expression is associated with chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), one of the glycosyltransferases that catalyzes the chain initiation and elongation of the CS backbone in its biosynthesis. Exogenous CS from cartilaginous fishes increased Csgalnact2 expression, although further studies are needed to confirm changes in CS biosynthesis. We observed reduced lipid accumulation in differentiated 3T3-L1 cells. Our findings highlight the role of CS polysaccharides, in inhibiting adipogenesis, even though further investigation is required to understand the underlying mechanism.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"77-86"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells. CFTR调节剂Elexacaftor/Tezacaftor/Ivacaftor对人支气管上皮细胞脂质代谢的影响。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-11 DOI: 10.1007/s10719-024-10174-7
Dorina Dobi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Giulia Lunghi, Massimo Aureli
{"title":"Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells.","authors":"Dorina Dobi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Giulia Lunghi, Massimo Aureli","doi":"10.1007/s10719-024-10174-7","DOIUrl":"10.1007/s10719-024-10174-7","url":null,"abstract":"<p><p>Cystic Fibrosis (CF) is a life-threatening hereditary disease resulting from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that encodes a chloride channel essential for ion transport in epithelial cells. Mutations in CFTR, notably the prevalent F508del mutation, impair chloride transport, severely affecting the respiratory system and leading to recurrent infections. Recent therapeutic advancements include CFTR modulators such as ETI, a combination of two correctors (Elexacaftor and Tezacaftor) and a potentiator (Ivacaftor), that can improve CFTR function in patients with the F508del mutation. This study investigated ETI's impact on the maturation of the mutated CFTR, the expression levels of its scaffolding proteins, and lipid composition of cells using bronchial epithelial cell lines expressing both wild-type and F508del CFTR. Our findings revealed that ETI treatment enhances CFTR and its scaffolding proteins expression and aids in rescuing mature F508del CFTR, causing also significant alterations in the lipid profile including reduced levels of lactosylceramide and increased content of gangliosides GM1 and GD1a. These changes were linked to ETI's influence on enzymes involved in the sphingolipid metabolism, in particular GM3 synthase and sialidase. Through this work, we aim to deepen understanding CFTR interactions with lipids, and to elucidate the mechanisms of action of CFTR modulators. Our findings may support the development of potential therapeutic strategies contributing to the ongoing efforts to design effective correctors and potentiators for CF treatment.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Inhibition of chondroitin sulphate-degrading enzyme Chondroitinase ABC by dextran sulphate. 硫酸葡聚糖对硫酸软骨素降解酶ABC的抑制作用。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-16 DOI: 10.1007/s10719-024-10175-6
Sagar Dalal, Rachana Pathak, Edward X S Moh, Nicolle H Packer
{"title":"Inhibition of chondroitin sulphate-degrading enzyme Chondroitinase ABC by dextran sulphate.","authors":"Sagar Dalal, Rachana Pathak, Edward X S Moh, Nicolle H Packer","doi":"10.1007/s10719-024-10175-6","DOIUrl":"10.1007/s10719-024-10175-6","url":null,"abstract":"<p><p>Chondroitin sulphate (CS) is a sulphated glycosaminoglycan (GAG) polysaccharide found on proteoglycans (CSPGs) in extracellular and pericellular matrices. Chondroitinase ABC (CSase ABC) derived from Proteus vulgaris is an enzyme that has gained attention for the capacity to cleave chondroitin sulphate (CS) glycosaminoglycans (GAG) from various proteoglycans such as Aggrecan, Neurocan, Decorin etc. The substrate specificity of CSase ABC is well-known for targeting various structural motifs of CS chains and has gained popularity in the field of neuro-regeneration by selective degradation of CS GAG chains. Within this context, our investigation into the biochemistry of CSase ABC led us to a previously unreported inhibition of CSase ABC activity by Dextran Sulphate (DexS). To understand the inhibitory effects of DexS, we compared its inhibition of CSase ABC to that of other polysaccharides such as Heparan Sulphate, Heparin, Colominic Acid, Fucoidan, and Dextran. This analysis identified key structural factors such as monosaccharide composition and linkage, sulphation degree and overall charge as influencing CSase ABC inhibition. Remarkably, DexS emerged as a unique inhibitor of CSase ABC, with distinctive inhibitory effects that correlate with its chain length. DexS has been used to reliably induce ulcerative colitis in mice, effectively mimicking inflammatory bowel diseases in humans, and has been previously shown to inhibit both RNA polymerase and reverse transcriptase. Our investigation emphasizes the interplay between the properties of DexS and CSase ABC, providing significant insights into the utilization of polysaccharide-based inhibitors for modulating enzyme activity.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"53-59"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
SUMOylated GLUT1 inhibited the glycometabolism disorder in chondroctyes during osteoarthritis. SUMOylated GLUT1抑制骨关节炎期间软骨细胞糖代谢紊乱。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-11 DOI: 10.1007/s10719-024-10176-5
Liwei Xiong
{"title":"SUMOylated GLUT1 inhibited the glycometabolism disorder in chondroctyes during osteoarthritis.","authors":"Liwei Xiong","doi":"10.1007/s10719-024-10176-5","DOIUrl":"10.1007/s10719-024-10176-5","url":null,"abstract":"<p><p>Reduction of glucose transporter 1 (GLUT1), even deletion, may results in cartilage fibrosis and osteoarthritis. This study aims to investigate the SUMOylation of GLUT1 in osteoarthritis through small ubiquitin-like modifier 1(SUMO1), and explore the role of SUMOylated GLUT1 in glycometabolism, proliferation and apoptosis in chondrocytes. Human chondrocytes were incubated with 10 ng/mL of IL-1β to mimic osteoarthritis in vitro. GLUT1, SUMO1 and Chondrocyte-related genes including COL2A1, MMP13 and ADAMTS4 were evaluated using western blot. Cell viability and cell apoptosis of chondrocytes were measured by cell counting kit-8 assay and flow cytometry, respectively. The changes in glycometabolism were evaluated using extracellular acidification rate (ECAR) and glucose uptake assay. Co-immunoprecipitation (Co-IP) was used to verify the interaction between GLUT1 and SUMO1. The stabilization role of SUMO1 in GLUT1 was determined by cycloheximide assay. IL-1β induced the decrease of GLUT1, cell viability, ECAR, glucose uptake and COL2A1 and the increase of cell apoptosis, MMP13 and ADAMTS4 in chondrocytes. However, overexpression of SUMO1 led to the reduction of cell apoptosis, MMP13 and ADAMTS4 and the elevation of GLUT1, cell viability, ECAR, glucose uptake and COL2A1 in IL-1β-stimulated chondrocytes. There was SUMOylation sites on GLUT1. Intriguingly, SUMO1 was significantly enriched in GLUT1 using Co-IP assay, and stabilized GLUT1 in chondrocytes. SUMO1-mediated SUMOylation is capable of stabilizing GLUT1 to inhibit glycometabilsm disorder and cell apoptosis in IL-1β-stimulated chondrocytes.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"41-52"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells. 淡水鱼废液硫酸软骨素/硫酸皮肤素对MC3T3-E1细胞成骨作用的机制研究。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1007/s10719-025-10178-x
Chandra Gavva, Kunal Sharan, Nandini Chilkunda
{"title":"Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells.","authors":"Chandra Gavva, Kunal Sharan, Nandini Chilkunda","doi":"10.1007/s10719-025-10178-x","DOIUrl":"10.1007/s10719-025-10178-x","url":null,"abstract":"<p><p>Glycosaminoglycans (GAGs) are essential bone extracellular matrix molecules that regulate osteoblast differentiation. Numerous studies have explored endogenous and exogenous GAG osteoanabolic activities using appropriate in vitro and in vivo models. However, GAGs' underlying the mechanism of action and structure-function relationships need to be elucidated in detail. Earlier, we showed that exogenous GAG can bring about osteogenesis in pre-osteoblast cells. In the present study, we have elucidated the mechanism of action of exogenous GAGs, especially of the chondroitin sulfate/dermatan sulfate (CS/DS) class on osteogenesis. GAGs were immobilized, and osteoblast differentiation was evaluated in MC3T3-E1 cells. Results indicated that GAGs supported osteoblast differentiation by promoting collagen production, extracellular matrix formation, and subsequent mineralization. We elucidated the mechanisms underlying these effects by assessing the key signaling molecules involved in osteogenesis in response to exogenous CS/DS with/without BMP2. CS/DS alone significantly increased pERK1/2 and ATF4 expression levels differentially in a time-dependent manner without significant effects on BMP2, RUNX2, and pSMAD5 protein expression. On the other hand, CS/DS, in the presence of BMP2, differentially increased BMP2, pSMAD5, pERK1/2, RUNX2, and ATF4 expression levels at various time points. Collectively, these results strongly suggest that CS/DS can promote osteogenesis, and in the presence of BMP2, it could promote SMAD-mediated ERK-dependent osteogenesis.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"15-26"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Spatial single-cell maps reveal ST6GAL1 promoting ovarian cancer metastasis. 空间单细胞图谱显示ST6GAL1促进卵巢癌转移。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI: 10.1007/s10719-025-10177-y
Lan-Hui Qin, Zijian Jiang, Chongze Yang, Rui Song, Pei-Yin Chen, Weihui Xu, Guanzhen Zeng, Jin-Yuan Liao, Liling Long
{"title":"Spatial single-cell maps reveal ST6GAL1 promoting ovarian cancer metastasis.","authors":"Lan-Hui Qin, Zijian Jiang, Chongze Yang, Rui Song, Pei-Yin Chen, Weihui Xu, Guanzhen Zeng, Jin-Yuan Liao, Liling Long","doi":"10.1007/s10719-025-10177-y","DOIUrl":"10.1007/s10719-025-10177-y","url":null,"abstract":"<p><p>In this study, spatial and single-cell transcriptome techniques were used to investigate the role of beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) in promoting peritoneal metastasis in ovarian cancer epithelial cells. We collected single-cell transcriptomic (GSE130000) and spatial transcriptomic datasets (GSE211956) from the Gene Expression Omnibus and RNA-sequencing data from The Cancer Genome Atlas. The Robust Cell Type Decomposition (RCTD) approach was implemented to integrate spatial and single-cell transcriptomic data. In addition, pseudo-time trajectory analysis, cell-cell communication networks, transcription factor activity profiling, spatial interaction mapping, and prognostic significance of gene expression were assessed. A significant enrichment of ST6GAL1 was observed in the epithelial cells of ovarian cancer, particularly in peritoneal metastases, which exhibited elevated metabolic activity compared to primary tumors. The levels of ST6GAL1 were significantly high in peritumoral and adjacent non-tumorous tissues, with increased metabolic activity, while the tumor core demonstrated ST6GAL1-negative epithelial cells. Extensive cell-cell communication and transcription factor networks were unraveled, potentially influencing vascular permeability and intracellular signaling. Clinically, high expression of ST6GAL1 in epithelial cells is associated with diminished progression-free survival, indicating its prognostic potential. In conclusion, ST6GAL1 is likely to significantly impact the progression and metastasis of ovarian cancer.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"27-40"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin. 硫酸聚糖抑制登革病毒包膜蛋白与肝素结合。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-12-01 Epub Date: 2024-12-16 DOI: 10.1007/s10719-024-10172-9
Jiyuan Yang, Payel Datta, Ke Xia, Vitor H Pomin, Chunyu Wang, Mingqiang Qiao, Robert J Linhardt, Jonathan S Dordick, Fuming Zhang
{"title":"Inhibition of sulfated glycans on the binding of dengue virus envelope protein to heparin.","authors":"Jiyuan Yang, Payel Datta, Ke Xia, Vitor H Pomin, Chunyu Wang, Mingqiang Qiao, Robert J Linhardt, Jonathan S Dordick, Fuming Zhang","doi":"10.1007/s10719-024-10172-9","DOIUrl":"10.1007/s10719-024-10172-9","url":null,"abstract":"<p><p>Dengue viruses (DENV) are transmitted to humans through mosquito bites and infect millions globally. DENV uses heparan sulfate (HS) for attachment and cell entry by binding the envelope protein to highly sulfated HS on target cells. Therefore, inhibiting the binding between DENV and HS could be a promising strategy for preventing DENV infection. In the current study, the interactions between DENV envelope protein (from Type 2 DENV) and heparin (a surrogate for HS) were analyzed using competition solution SPR. Results demonstrate that heparin binds to DENV envelope protein with high affinity (K<sub>D</sub> = 8.83 nM). Competitive Solution SPR assays using surface-immobilized heparin and a series of naturally-sourced and semi-synthetic sulfated glycans demonstrated significant inhibitory activity against the binding of DENV envelope proteins to heparin. This study of molecular interactions could provide insights into the development of therapeutics for DENV infection.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"371-380"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain. 从与 Fc 结构域融合的不依赖阳离子的甘露糖-6-磷酸受体中生成结构域 9。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI: 10.1007/s10719-024-10169-4
Yu-He Tang, Yi-Shi Liu, Morihisa Fujita
{"title":"Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain.","authors":"Yu-He Tang, Yi-Shi Liu, Morihisa Fujita","doi":"10.1007/s10719-024-10169-4","DOIUrl":"10.1007/s10719-024-10169-4","url":null,"abstract":"<p><p>Lysosomal storage diseases (LSDs) are genetic disorders caused by mutations in lysosomal enzymes, lysosomal membrane proteins or genes related to intracellular transport that result in impaired lysosomal function. Currently, the primary treatment for several LSDs is enzyme replacement therapy (ERT), which involves intravenous administration of the deficient lysosomal enzymes to ameliorate symptoms. The efficacy of ERT largely depends on the mannose-6-phosphate (M6P) modification of the N-glycans associated with the enzyme, as M6P is a marker for the recognition and trafficking of lysosomal enzymes. In cells, N-glycan processing and M6P modification occur in the endoplasmic reticulum and Golgi apparatus. This is a complex process involving multiple enzymes. In the trans-Golgi network (TGN), M6P-modified enzymes are recognized by the cation-independent mannose-6-phosphate receptor (CIMPR) and transported to the lysosome to exert their activities. In this study, we used the 9th domain of CIMPR, which exhibits a high affinity for M6P binding, and fused it with the Fc domain of human immunoglobulin G<sub>1</sub> (IgG<sub>1</sub>). The resulting fusion protein specifically binds to M6P-modified proteins. This provides a tool for the rapid detection and concentration of M6P-containing recombinant enzymes to assess the effectiveness of ERT. The advantages of this approach include its high specificity and sensitivity and may lead to the development of new treatments for LSDs.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"395-405"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Processing of N-glycans in the ER and Golgi influences the production of surface sialylated glycoRNA. ER 和高尔基体中 N-聚糖的加工会影响表面糖基化的 glycoRNA 的产生。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2024-12-01 Epub Date: 2024-11-12 DOI: 10.1007/s10719-024-10171-w
Yi-Shi Liu, Yu-Long Miao, Yue Dou, Ze-Hui Yang, Wenhao Sun, Xiaoman Zhou, Zijie Li, Nakanishi Hideki, Xiao-Dong Gao, Morihisa Fujita
{"title":"Processing of N-glycans in the ER and Golgi influences the production of surface sialylated glycoRNA.","authors":"Yi-Shi Liu, Yu-Long Miao, Yue Dou, Ze-Hui Yang, Wenhao Sun, Xiaoman Zhou, Zijie Li, Nakanishi Hideki, Xiao-Dong Gao, Morihisa Fujita","doi":"10.1007/s10719-024-10171-w","DOIUrl":"10.1007/s10719-024-10171-w","url":null,"abstract":"<p><p>Glycoconjugates, including glycans on proteins and lipids, have obtained significant attention due to their critical roles in both intracellular and intercellular biological functions and processes. Notably, recent discoveries have revealed the presence of glycosylated RNAs (glycoRNAs) on cell surfaces. Despite the well-characterized roles of RNA modifications, RNA glycosylation remains relatively unexplored. In this study, we investigate the relationship between N-glycosylation and RNA glycosylation. Using a recombinant Siglec11-Fc as a probe, we detected surface sialylated glycoRNAs in human cell lines and identified their dependency on the catalytic isoforms of the oligosaccharyltransferase (OST) complex, implicating STT3A-dependent protein glycosylation as a predominant contributor for affecting indirect generation of glycoRNAs. Additionally, perturbations in N-glycan biosynthesis pathways or changes in N-glycan structure impact surface sialylated glycoRNA levels, indicating a regulatory role of glycan metabolic pathways in RNA glycosylation. Together, our results underscore the intricate relationship between protein N-glycosylation and processing and RNA biology.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"361-370"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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