Biochemical Society transactions最新文献_第3页

Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders. 神经发育障碍患者内质网蛋白平衡紊乱。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253035

Danilo B Medinas, Nayrob Pereira, Rodolfo Pereira, Giovanna R da Silva, Victor H S Santos

{"title":"Disturbances of endoplasmic reticulum proteostasis in neurodevelopmental disorders.","authors":"Danilo B Medinas, Nayrob Pereira, Rodolfo Pereira, Giovanna R da Silva, Victor H S Santos","doi":"10.1042/BST20253035","DOIUrl":"10.1042/BST20253035","url":null,"abstract":"The endoplasmic reticulum (ER) is a vital organelle involved in the biogenesis of membrane and secreted proteins. Proteostasis (protein homeostasis) in the ER relies on finely co-ordinated mechanisms for translocation of polypeptides from the cytosol to the organelle lumen and membrane, introduction of co- and post-translational modifications, protein folding and quality control, exportation of mature proteins and disposal of unfolded or aggregated species, besides the regulation of gene expression to adjust the proteostasis network to the cellular demands for protein biogenesis. Neurodevelopmental processes involving neurogenesis, neuronal migration and differentiation, neural circuit wiring, synaptogenesis, among others, require extensive proteome diversification and remodeling, with high fluxes through the secretory pathways constantly challenging ER proteostasis. Genetic defects affecting the different nodes of the ER proteostasis network can severely disturb neurodevelopment. Here, we compile evidence illustrating how perturbations to the different steps of protein biogenesis in the ER can lead to neurological disorders and present major questions to guide research in the field.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"897-907"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727167","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

The rise of AMPylation: from bacterial beginnings to modern implications in health and disease. ampyation的兴起：从细菌起源到健康和疾病的现代含义。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253056

Meghomukta Mukherjee, Anju Sreelatha

引用次数: 0

RAS-membrane interaction and oligomerization: there is more than meets the eye. ras -膜相互作用和寡聚化：有更多的满足眼睛。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253030

Abraham C Sianoya, Vijay K Bhardwaj, Alemayehu A Gorfe

引用次数: 0

Mechanisms of fusidic acid resistance. 耐夫西地酸机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253064

Adrián González-López, Maria Selmer

{"title":"Mechanisms of fusidic acid resistance.","authors":"Adrián González-López, Maria Selmer","doi":"10.1042/BST20253064","DOIUrl":"10.1042/BST20253064","url":null,"abstract":"Fusidic acid (FA) is an antibiotic used to treat staphylococcal infections, particularly Staphylococcus aureus. It acts by inhibiting protein synthesis through locking elongation factor G (EF-G) to the ribosome. In S. aureus, there are three mechanisms of resistance. Mutations in the antibiotic target, EF-G (fusA), are common. These mutations affect the FA binding or the stability of the FA-locked state of EF-G but, due to effects on the normal function of EF-G, impose a fitness cost for the pathogen. The most common mechanism, FusB-type, involves expression of a resistance protein, FusB or FusC (FusD or FusF in other staphylococci), that provides target protection. The resistance protein binds to EF-G in its FA-locked state and mediates its release from the ribosome. An uncommon resistance mechanism (FusE) involves mutations in a ribosomal protein, uL6. In other bacteria, outside of its current clinical use, resistance to FA involves efflux pumps, limited membrane permeability, or enzymes that chemically alter FA. On a global level, the prevalence of FA resistance is relatively low, indicating that the antibiotic remains effective.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"1011-1022"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871250","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

The exit from naive pluripotency: a platform for the study of enhancer mechanistics. 从幼稚多能性的退出：一个研究增强子机制的平台。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253037

Mattias Enar Jonasson, Christa Buecker

引用次数: 0

Molecular insight on the role of the phosphoinositide PIP3 in regulating the protein kinases Akt, PDK1, and BTK. 磷酸肌肽PIP3在调节蛋白激酶Akt， PDK1和BTK中的分子作用。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-29 DOI: 10.1042/BST20253059

Alexandria L Shaw, John E Burke

{"title":"Molecular insight on the role of the phosphoinositide PIP3 in regulating the protein kinases Akt, PDK1, and BTK.","authors":"Alexandria L Shaw, John E Burke","doi":"10.1042/BST20253059","DOIUrl":"10.1042/BST20253059","url":null,"abstract":"Protein kinases are master regulators of myriad processes in eukaryotic cells playing critical roles in growth, metabolism, cellular differentiation, and motility. A subclass of protein kinases is regulated by their ability to be localized and activated by the phosphoinositide phosphatidylinositol (3,4,5)-trisphosphate (PIP3). This includes multiple members of the AGC and TEC family kinases, which contain PIP3 binding pleckstrin homology (PH) domains. It has been postulated that they can be activated by PIP3-mediated disruption of autoinhibitory interactions between their kinase domains and PH domains. There has been considerable controversy based on differing molecular models for how these kinases are regulated by lipid binding and post-translational modifications. This review focuses on understanding the molecular underpinnings for how the PH domains of these enzymes regulate kinase activity and what role PIP3 plays in pathway activation. A specific focus is on the integration of experimental data derived from X-ray crystallography, cryo-electron microscopy, and hydrogen deuterium exchange mass spectrometry along with recent advances in artifical intelligence enabled protein modeling. The main lipid-binding enzymes described are the AGC protein kinases 3-phosphoinositide-dependent kinase (PDK1) and Akt, and the TEC family kinase, Bruton's agammaglobulinemia tyrosine kinase (BTK).","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":"737-749"},"PeriodicalIF":4.3,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558918","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

Regulation of early gonocyte differentiation in zebrafish. 斑马鱼早期性腺细胞分化的调控。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-26 DOI: 10.1042/BST20253046

Miranda L Wilson, Florence L Marlow

{"title":"Regulation of early gonocyte differentiation in zebrafish.","authors":"Miranda L Wilson, Florence L Marlow","doi":"10.1042/BST20253046","DOIUrl":"10.1042/BST20253046","url":null,"abstract":"Zebrafish have been and continue to be an important model organism for studies of fundamental biology and biomedicine, including reproductive development and the cell intrinsic and extrinsic mechanisms regulating early gonocyte differentiation. Wild zebrafish strains determine sex using a ZW genetic system wherein the maternally inherited sex chromosome determines the embryo's sex. Like other species, including humans, regulation of conserved autosomal genes is crucial for gonocyte and sexual differentiation. How these conserved factors are regulated by the diverse mechanisms found throughout the animal kingdom is an active area of investigation. Domesticated zebrafish strains lack the ZW sex determination system found in wild strains and undergo gonocyte and sexual differentiation through a process exclusively governed by autosomal genes and nongenetic influences like environmental factors. Through mutational analysis, molecular genetics, and RNA sequencing, our understanding of the complexity of oocyte and spermatocyte differentiation has become clearer. In this review, we explore the most recent studies of the conserved and divergent mechanisms of gonocyte differentiation between wild and domesticated zebrafish as well as possible adaptations related to their domestication. Further, the contributions of individual genes and their molecular genetic hierarchy in regulating gonocyte differentiation are discussed and related to other species where relevant. We also address the recent characterization of a novel oocyte-progenitor and its potential implications in gonad differentiation. Finally, the role of gonocyte-extrinsic mechanisms, specifically communication between differentiating gonocytes and surrounding somatic gonad cells and the influence of resident and infiltrating immune cells, is discussed.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940778","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

Translation stalling in neurons: a critical mechanism for timely protein delivery to distal cellular processes. 翻译停滞在神经元：蛋白质及时传递到远端细胞过程的关键机制。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-26 DOI: 10.1042/BST20253066

Jingyu Sun, Lily Drever, Joaquin Ortega, Wayne S Sossin

{"title":"Translation stalling in neurons: a critical mechanism for timely protein delivery to distal cellular processes.","authors":"Jingyu Sun, Lily Drever, Joaquin Ortega, Wayne S Sossin","doi":"10.1042/BST20253066","DOIUrl":"10.1042/BST20253066","url":null,"abstract":"Neurons require local protein synthesis at synapses to control their proteome in response to local inputs. Work over the past two decades has revealed that neurons can use a specialized mechanism to transfer mRNAs and ribosomes to local sites in addition to canonical mechanisms used in many cell types. Neurons initiate translation on the ribosomes in the cellular soma, pause the process, and then package these stalled ribosomes into structures known as 'neuronal RNA granules' that are transported to synapses. This review provides an overview of recent studies that characterize these ribosomes/granules biochemically and structurally. These studies provide novel insights into the unique and specialized characteristics of neuronal ribosomes that facilitate this distinct transport mechanism. Many questions remain, including the influence of mRNA sequences on the stalling process and how ribosomes in the granules avoid the physiological responses that, in other cells, recycle ribosomal subunits upon stalling. Many neurodevelopmental disorders, such as autism and intellectual disability, occur when local translation is disrupted in neurons. Understanding mechanisms underlying the stalling of neuronal ribosomes, their transport to processes, and their reactivation may enable novel therapies for neurodevelopmental diseases.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940691","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

Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease. 发电厂的质量控制：线粒体蛋白酶平衡功能障碍和疾病。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-26 DOI: 10.1042/BST20253044

Megan J Baker, Kai Qi Yek, Diana Stojanovski

引用次数: 0

Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance. 分枝杆菌HflX的多面作用：核糖体分裂、rRNA紊乱和耐药性。

IF 4.3 3区生物学

Biochemical Society transactions Pub Date : 2025-08-20 DOI: 10.1042/BST20253084

Soneya Majumdar, Pallavi Ghosh, Rajendra K Agrawal

{"title":"Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance.","authors":"Soneya Majumdar, Pallavi Ghosh, Rajendra K Agrawal","doi":"10.1042/BST20253084","DOIUrl":"10.1042/BST20253084","url":null,"abstract":"High frequency of lysogenization X (HflX) is an enigmatic protein that has been implicated in rescuing translationally stalled ribosomes and macrolide-lincosamide antibiotic resistance, as well as in ribosome biogenesis. The protein shows significant sequence and structural variation across species, including variation among paralogs within the same organism. Recent cryo-EM structure determination of ribosome-HflX complexes from different eubacterial species has provided important mechanistic clues to HflX function. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared with their eubacterial homologs, suggesting that the mycobacterial HflX could have distinct functional mechanisms. This article presents a brief overview of these studies highlighting (i) what we have learned from recent multiple mycobacterial ribosome-HflX complex structures and (ii) the roles of mycobacteria-specific segments in ribosomal RNA disordering that leads to ribosome splitting to rescue translation by removing the drug-bound stalled ribosome from the translationally active polysome pool. Future studies needed to resolve some of the outstanding issues related to HflX function and dynamics are also discussed.","PeriodicalId":8841,"journal":{"name":"Biochemical Society transactions","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12493154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940728","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