Sub-cellular biochemistry最新文献

{"title":"Energy-Dependent Urea Transports in Mammals and their Functional Consequences.","authors":"Lise Bankir, Gilles Crambert","doi":"10.1007/978-981-96-6898-4_10","DOIUrl":"https://doi.org/10.1007/978-981-96-6898-4_10","url":null,"abstract":"<p><p>In lower organisms (bacteria, fungi, yeast), some species that express the enzyme urease take up urea from the surrounding medium as a source of nitrogen, by energy-dependent urea transporters. In contrast, in mammals, urea is an endproduct of nitrogen metabolism, and the energy-dependent urea transports are associated with either the need to excrete nitrogen efficiently, in the case of excess nitrogen intake, or the need to conserve nitrogen and re-use it, in the case of low nitrogen supply.Three different energy-dependent urea transports have been characterized functionally in the mammalian kidney. One responsible for urea secretion in the straight segment of the proximal tubule (proximal straight tubule, PST), another for urea reabsorption in the upper third of the inner medullary collecting duct (IMCD), and one in the very late portion of the IMCD. But intriguingly, up to now, none of the membrane transporters responsible for these transports has been characterized molecularly.This review describes these urea transports functionally and proposes a candidate transporter responsible for urea secretion in the PST. Based on the study of knockout mice, SLC6A18 has been characterized as a glycine transporter, but several previous observations suggest that it may also serve another function. SLC6A18 is very likely a urea/glycine, sodium-dependent antiport. These observations are described in detail.Energy-dependent urea transport is suspected to also take place in two other organs that express facilitated urea transporters; in the testis, urea secretion could initiate a flux of fluid in seminiferous tubules to ensure sperm transport into the lumen; in the bladder, urea secretion could reclaim urea that is at permanent risk of dissipation, due to the large urea concentration difference between urine and blood and the high expression of the facilitated transporter UT-B on the basal membrane of the urothelium.The energy-dependent secretion of urea in the PST has a number of consequences. (1) It allows a better efficiency of urea excretion and thus may prevent some toxicity of urea. (2) It provides a much better understanding of the urine concentrating mechanism. (3) It explains how urea may influence glomerular filtration rate, indirectly.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"118 ","pages":"193-228"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Structures of Urea Transporters.","authors":"Mengyao Xiong, Shenming Huang, Jinpeng Sun, Baoxue Yang","doi":"10.1007/978-981-96-6898-4_2","DOIUrl":"https://doi.org/10.1007/978-981-96-6898-4_2","url":null,"abstract":"<p><p>Urea transporters (UTs) facilitate the rapid transport of urea from the extracellular space to the intracellular space through a selective transport mechanism driven by urea concentration gradients. Advances in Cryo-electron microscopy and X-ray crystallography have enabled us to solve the homotrimer structures of UT-A and UT-B, which share a common feature comprising two homologous domains surrounding a continuous transmembrane pore, indicating that UTs transport urea via a channel-like mechanism. By analyzing the structures of ligand-protein complexes, results from molecular dynamics simulations, and functional data on urea analogues and small molecule permeation inhibitors, we can gain a deeper understanding of the conservation and specificity of the urea channel architecture, and clearly recognize how urea is transported by UTs and the mechanisms of small molecule inhibition. This will provide an important structural basis for drug design and development.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"118 ","pages":"19-43"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urea Transport Mediated by Membrane Proteins of Non-urea-Transporters.","authors":"Minghui Wang, Weidong Wang, Chunling Li","doi":"10.1007/978-981-96-6898-4_9","DOIUrl":"https://doi.org/10.1007/978-981-96-6898-4_9","url":null,"abstract":"<p><p>Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues of mammals. Urea is then eliminated through fluids, especially urine. Urea also serves as a readily available nitrogen source for the growth of many organisms, including plants and bacteria. Urea transporters are recognized as the primary membrane proteins responsible for urea transport in organisms. However, an increasing body of studies has identified additional membrane proteins in animals, plants, and microbes that exhibit urea transport capabilities or potential. The contribution of these membrane proteins to the maintenance of physiological homeostasis and their interactions with urea transporters remains to be fully elucidated. In this chapter, transport, characteristics, regulation, as well as cellular localization of non-urea-transporter membrane proteins facilitating urea transport, are reviewed to highlight their roles in physiology and pathophysiology. Specifically, the mammalian aquaporins AQP3, AQP6, AQP7, AQP8, AQP9, AQP10, and a sodium-glucose transporter (SGLT1) in the kidney are permeable to urea. In plants, tonoplast intrinsic proteins (TIPs), a member of aquaporin family, and the DUR3 orthologue, potentially play roles in low- and high-affinity urea transport, respectively. Two urea transporters pH-independent (Yut) and pH-dependent transporters (ureI) in bacteria are known to play roles in disease conditions.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"118 ","pages":"167-191"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urea Transporters and Their Gene Mutations in Diseases.","authors":"Boyue Huang, Hongkai Wang, Jiaoyu Hou, Jianhua Ran","doi":"10.1007/978-981-96-6898-4_7","DOIUrl":"https://doi.org/10.1007/978-981-96-6898-4_7","url":null,"abstract":"<p><p>Urea transporters (UTs) UT-As (encoded by Slc14A2) and UT-B (encoded by Slc14A1), are important members of the solute carrier family. They are a group of membrane channel proteins that are selectively permeable to urea. Slc14A1 is considered the key gene determining the Kidd blood group system, and its variants can lead to the loss of Jk antigens, resulting in transfusion-related complications. Additionally, studies have shown that Slc14A1 is closely associated with cancer development and progression, with its expression level and promoter methylation status potentially serving as biomarkers for cancer progression and prognosis. Recent research suggests that UT-B functional deficiency may cause neurodegenerative diseases by accumulating urea in the brain, thereby affecting neuronal function and viability. Mutations of Slc14A2 are linked to hypertension and metabolic syndrome, due to its essential role in maintaining urea homeostasis. This chapter aims to introduce the clinical significance of UT-B and UT-A and highlight their potential roles as diagnostic and therapeutic targets.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"118 ","pages":"127-140"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Trajectories in Human Prion Diseases.","authors":"Maria Letizia Barreca, Emiliano Biasini","doi":"10.1007/978-3-031-97055-9_5","DOIUrl":"https://doi.org/10.1007/978-3-031-97055-9_5","url":null,"abstract":"<p><p>Prion diseases are rare yet devastating neurodegenerative disorders that result from the misfolding of the cellular prion protein, PrP^C, into its infectious and pathogenic isoform, PrP^Sc. These diseases are marked by progressive neuronal damage, leading to irreversible cognitive and motor impairments and, ultimately, death. Despite extensive research into their underlying mechanisms, effective treatments for prion diseases remain elusive. Such a lack of effective therapies mainly arises from several challenges, including delayed diagnosis and the complex and poorly understood biology of prion neurotoxicity.This chapter provides an in-depth exploration of current and emerging therapeutic strategies to treat prion diseases. One promising approach involves using small molecules to inhibit prion replication by destabilizing PrP^Sc or modulating PrP^C homeostasis, possibly avoiding previously observed strain-dependent drug resistance. In parallel, immunotherapeutic approaches, including passive and active immunization, have shown potential in targeting prions. However, challenges related to brain penetration and potential neurotoxicity remain significant hurdles to their successful clinical application. Developing advanced genetic tools, such as RNA interference (RNAi) and CRISPR-based technologies, has opened up new avenues for therapeutic intervention. These approaches selectively target and reduce PrP^C expression, thereby preventing the formation and accumulation of PrP^Sc. The chapter also highlights the progress in clinical trials, such as the PrProfile trial for ION717, which tests a novel treatment based on an antisense oligonucleotide (ASO). As we look toward the future, the chapter underscores the need for a multifaceted approach to treating prion diseases. Furthermore, early detection methods, innovative drug delivery systems, and collaborative interdisciplinary research efforts will be essential for translating scientific discoveries into practical clinical breakthroughs.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"112 ","pages":"91-113"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Crowing in Nuclear Pore.","authors":"Masahiro Kumeta","doi":"10.1007/978-3-032-03370-3_12","DOIUrl":"https://doi.org/10.1007/978-3-032-03370-3_12","url":null,"abstract":"<p><p>Nuclear pores serve as the sole gates mediating nucleocytoplasmic molecular communication. They constantly accept heavy molecular traffic at a rate of ~1000 molecules per second, selected from a vast number of molecules randomly approaching the pores. The central channel of the pores are highly crowded with an intrinsically disordered region of pore-forming subunits and this channel functions as a selective permeability barrier. Recently, the phase separation properties of the hydrophobic subunits of pores have been reported, together with the flexible amphiphilic nature of the transporting molecules. These findings suggest that phase separation is a fundamental mechanism of action in nuclear pores. In this chapter, the entire nucleocytoplasmic transport system and composition of the nuclear pore complex are reviewed, followed by a detailed review of recent studies focusing on the characteristic features of both nuclear pores and transporting molecules. Finally, intrinsic and extrinsic factors that adaptively affect the function of the molecular crowding barrier are introduced.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"109 ","pages":"257-272"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneity of Molecular Crowding and Liquid-Liquid Phase Separation.","authors":"Mitsuki Tsuruta, Sumit Shil, Keiko Kawauchi, Daisuke Miyoshi","doi":"10.1007/978-3-032-03370-3_15","DOIUrl":"https://doi.org/10.1007/978-3-032-03370-3_15","url":null,"abstract":"<p><p>The inside of a living cell is highly crowded with extremely diverse biomacromolecules, small metabolites and osmolytes. The molecular conditions in cells change dynamically and rapidly depending on the cell cycle and state, organelle, and compartment. Much remains unknown regarding how biomolecular interactions and reactions can proceed in a spatiotemporally specific manner in such crowded, heterogeneous, and dynamic molecular environments. Selective condensation/droplet formation of biomolecules via liquid-liquid phase separation may be critical for interactions and reactions inside cells. In this chapter, we briefly describe the heterogeneity of molecular environments inside cells and the biological roles of liquid-liquid phase separation that allows biomolecular interactions and reactions in such heterogenous molecular environments. Finally, we discuss the mutual relationship between molecular crowding and liquid-liquid phase separation.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"109 ","pages":"327-345"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis of Prion Diseases.","authors":"Tayyaba Saleem, Anna-Lisa Fischer, Sezgi Canaslan, Susana Da Silva Correia, Peter Hermann, Matthias Schmitz, Angela Da Silva Correia, Inga Zerr","doi":"10.1007/978-3-031-97055-9_2","DOIUrl":"https://doi.org/10.1007/978-3-031-97055-9_2","url":null,"abstract":"<p><p>Prion diseases are rapidly progressive and fatal neurodegenerative disorders caused by misfolded prion proteins. Accurate and early diagnosis is essential to distinguish these conditions from treatable dementias and to prevent iatrogenic transmission. While definitive confirmation still depends on postmortem neuropathological techniques such as immunohistochemistry and western blot, recent advances have significantly improved antemortem diagnostic capabilities. The antemortem diagnosis combines clinical evaluation, neuroimaging, electroencephalography, and cerebrospinal fluid biomarkers. The development of real-time quaking-induced conversion (RT-QuIC) has enhanced the detection of misfolded prion proteins with high specificity, complementing existing diagnostic methods. Although advancements in biomarkers and diagnostic methodologies have improved the early detection of prion diseases, challenges remain. Continued research is crucial for enhancing early identification, tracking disease progression, optimizing patient management, and further elucidating disease pathogenesis.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"112 ","pages":"15-38"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Expression of Lamins and Modulation of Chromatin Architecture in Carcinogenesis: tous pour un et un pour tous.","authors":"Shreyasi Dey Sarkar, Duhita Sengupta, Kaushik Sengupta","doi":"10.1007/978-3-032-00537-3_5","DOIUrl":"10.1007/978-3-032-00537-3_5","url":null,"abstract":"<p><p>Lamins are intermediate filament proteins of the nucleus that are present in nuclear lamina as well as nucleoplasm. They play diverse roles in maintaining the structure and rigidity of the nucleus as well as nuclear homeostasis. Lamins are of two main types-A and B. B-type lamins are expressed from the embryonic stage, whereas A-type lamins are expressed during cell differentiation. Both A- and B-type lamins form distinct but interacting networks that contribute to differential chromosome tethering and distribution within the nucleus. A- and B-type lamins maintain the euchromatin-to-heterochromatin ratio in health and disease. Interestingly, lamin A/B itself varies largely and distinctly in different types of cancer. Likewise, the lamina-associated domains of the chromatin network get significantly altered in the process of carcinogenesis. We have discussed here the differential expression of lamin proteins in different cancers, contributing to distinct genome organization, ultimately precipitating into diverse neoplastic transformation.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"115 ","pages":"117-141"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reshuffling Overcrowded Milieu: Stress-Induced Reorganization of the Eukaryotic Membrane-Less Organelles.","authors":"Anastasia A Gavrilova, Eva A Shmidt, Vladimir N Uversky, Alexander V Fonin","doi":"10.1007/978-3-032-03370-3_16","DOIUrl":"10.1007/978-3-032-03370-3_16","url":null,"abstract":"<p><p>Cells are crowded entities, but the intracellular space represents an inhomogeneously crowded environment, where the concentrations of macromolecules (proteins, nucleic acids, etc.) are not uniformly distributed throughout the cell resulting in regions with different levels of crowding. Liquid-liquid phase separation (LLPS)-driven formation of various membrane-less organelles (MLOs) represents a means for the control, regulation, and redistribution of cellular crowded environment. Because MLOs contain the high concentrations of biological macromolecules (proteins and RNAs), often significantly exceeding those of the surrounding cytoplasm or nucleoplasm, their inside represents an overcrowded milieu. It is well-known that the appearance of the stress-induced MLOs represents a reaction to various types of stresses, enabling the protection of the genetic and protein material during hostile conditions. However, stress can also cause structural, functional, and compositional changes in the MLOs, which are constitutively present in the cells, thereby causing the reshuffling of the overcrowded environment. This chapter describes stress-induced changes in several MLOs (nucleolus, Cajal bodies, paraspeckles, nuclear speckles, NELF-Bodies, nucleolar stress bodies, PML-bodies, stress-granules, and Р-bodies) found in the eukaryotic cells.</p>","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"109 ","pages":"347-373"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}