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Vitamins and Hormones 2020Water can diffuse freely through the lipid bilayer at a limited rate or by water channel proteins in a rapid speed. Aquaporins (AQPs) are a family of membrane water... (Review)
Review
Water can diffuse freely through the lipid bilayer at a limited rate or by water channel proteins in a rapid speed. Aquaporins (AQPs) are a family of membrane water channel proteins that mainly function as regulators of intracellular and intercellular water flow. They are distributed wildly in specific cell types in multiple organs and tissues. Since the first AQP was identified, 13 AQPs have been characterized in mammals. Structural analysis shows that AQPs are homotetramers with each AQP monomer containing six transmembrane α-helices, two half helices and five connecting loops with two conserved asparagine-proline-alanine (NPA) motifs embedding into the plasma membrane. AQPs are demonstrated to selectively transport water but also some other small molecules. The cellular functions of aquaporins are regulated mainly by posttranslational modifications, e.g., phosphorylation, ubiquitination, glycosylation, subcellular distribution, degradation, and protein interactions. Aquaporins, in particular, AQP2 plays an important role in some disease conditions such as water loss and gain. Insights into the molecular mechanisms regulating AQPs and its clinical significance are proving to be fundamental for development of novel therapeutic targets or reliable diagnostic and prognostic biomarkers. In this chapter, we summarize the molecular aspects of aquaporins which include the isoforms, crystal structure and the molecular mechanisms underlying the regulation of AQPs, with most focus on arginine vasopressin-regulated AQP2.
Topics: Aquaporins; Humans; Phosphorylation; Protein Structure, Secondary
PubMed: 32138947
DOI: 10.1016/bs.vh.2019.08.019 -
Advances in Experimental Medicine and... 2023Water transport through membrane is so intricate that there are still some debates. AQPs are entirely accepted to allow water transmembrane movement depending on osmotic...
Water transport through membrane is so intricate that there are still some debates. AQPs are entirely accepted to allow water transmembrane movement depending on osmotic gradient. Cotransporters and uniporters, however, are also concerned in water homeostasis. UT-B has a single-channel water permeability that is similar to AQP1. CFTR was initially thought as a water channel but now not believed to transport water directly. By cotransporters, such as KCC4, NKCC1, SGLT1, GAT1, EAAT1, and MCT1, water is transported by water osmosis coupling with substrates, which explains how water is transported across the isolated small intestine. This chapter provides information about water transport mediated by other membrane proteins except AQPs.
Topics: Aquaporins; Biological Transport; Membrane Proteins; Permeability; Water; Aquaporin 1
PubMed: 36717505
DOI: 10.1007/978-981-19-7415-1_23 -
Advances in Experimental Medicine and... 2023There are at least eight aquaporins (AQPs) expressed in the kidney. Including AQP1 expressed in proximal tubules, thin descending limb of Henle and vasa recta; AQP2,...
There are at least eight aquaporins (AQPs) expressed in the kidney. Including AQP1 expressed in proximal tubules, thin descending limb of Henle and vasa recta; AQP2, AQP3, AQP4, AQP5, and AQP6 expressed in collecting ducts; AQP7 expressed in proximal tubules; AQP8 expressed in proximal tubules and collecting ducts; and AQP11 expressed in the endoplasmic reticulum of proximal tubular epithelial cells. Over years, researchers have constructed different AQP knockout mice and explored the effect of AQP knockout on kidney function. Thus, the roles of AQPs in renal physiology are revealed, providing very useful information for addressing fundamental questions about transepithelial water transport and the mechanism of near isoosmolar fluid reabsorption. This chapter introduces the localization and function of AQPs in the kidney and their roles in different kidney diseases to reveal the prospects of AQPs in further basic and clinical studies.
Topics: Mice; Animals; Aquaporin 2; Aquaporins; Kidney; Kidney Diseases; Kidney Tubules, Proximal; Mice, Knockout
PubMed: 36717493
DOI: 10.1007/978-981-19-7415-1_11 -
Advances in Experimental Medicine and... 2023Aquaporins (AQPs) are water channel proteins facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland...
Aquaporins (AQPs) are water channel proteins facilitating fluid transport in alveolar space, airway humidification, pleural fluid absorption, and submucosal gland secretion. In this chapter, we mainly focus on the expression of four AQPs in the lungs, which include AQP1, AQP2, AQP4, and AQP5 in normal and disease status, and the experience of AQPs function from various model and transgenic mice were summarized in detail to improve our understanding of the role of AQPs in fluid balance of respiratory system. It has been suggested that AQPs play important roles in various physiology and pathophysiology conditions of different lung diseases. There still remains unclear the exact role of AQPs in lung diseases, and thus continuous efforts on elucidating the roles of AQPs in lung physiological and pathophysiological processes are warranted.
Topics: Mice; Animals; Aquaporin 2; Aquaporins; Lung; Mice, Transgenic; Biological Transport; Lung Diseases
PubMed: 36717491
DOI: 10.1007/978-981-19-7415-1_9 -
Biological Chemistry May 2020Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site... (Review)
Review
Mitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site for precursor proteins that are produced on cytosolic ribosomes. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membranes, the intermembrane space, and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel (VDAC), in mitochondrial protein biogenesis. Porin forms the major channel for metabolites and ions in the outer membrane of mitochondria. Two different functions of porin in protein translocation have been reported. First, it controls the formation of the TOM complex by modulating the integration of the central receptor Tom22 into the mature translocase. Second, porin promotes the transport of carrier proteins toward the carrier translocase (TIM22 complex), which inserts these preproteins into the inner membrane. Therefore, porin acts as a coupling factor to spatially coordinate outer and inner membrane transport steps. Thus, porin links metabolite transport to protein import, which are both essential for mitochondrial function and biogenesis.
Topics: Humans; Mitochondria; Mitochondrial Proteins; Porins; Protein Transport; Saccharomyces cerevisiae
PubMed: 31967957
DOI: 10.1515/hsz-2019-0438 -
Advances in Experimental Medicine and... 2023Aquaporins (AQPs) mediate the bidirectional water flow driven by an osmotic gradient. Either gating or trafficking allows for rapid and specific AQP regulation in a... (Review)
Review
Aquaporins (AQPs) mediate the bidirectional water flow driven by an osmotic gradient. Either gating or trafficking allows for rapid and specific AQP regulation in a tissue-dependent manner. The regulatory mechanisms of AQP2 are discussed mainly in this chapter, as the mechanisms controlling the regulation and trafficking of AQP2 have been very well studied. The targeting of AQP2 to the apical plasma membrane of collecting duct principal cells is mainly regulated by the action of arginine vasopressin (AVP) on the type 2 AVP receptor (V2R), which cause increased intracellular cAMP or elevated intracellular calcium levels. Activation of these intracellular signaling pathways results in vesicles bearing AQP2 transport, docking and fusion with the apical membrane, which increase density of AQP2 on the membrane. The removal of AQP2 from the membrane requires dynamic cytoskeletal remodeling. AQP2 is degraded through the ubiquitin proteasome pathway and lysosomal proteolysis pathway. Finally, we review updated findings in transcriptional and epigenetic regulation of AQP2.
Topics: Aquaporin 2; Epigenesis, Genetic; Kidney Tubules, Collecting; Aquaporins; Cell Membrane; Signal Transduction
PubMed: 36717485
DOI: 10.1007/978-981-19-7415-1_3 -
Advances in Experimental Medicine and... 2023In this chapter, we mainly discuss the expression and function of aquaporins (AQPs) expressed in digestive system. AQPs are highly conserved transmembrane protein...
In this chapter, we mainly discuss the expression and function of aquaporins (AQPs) expressed in digestive system. AQPs are highly conserved transmembrane protein responsible for water transport across cell membranes. AQPs in gastrointestinal tract include four members of aquaporin subfamily: AQP1, AQP4, AQP5, and AQP8, and three members of aquaglyceroporin subfamily: AQP3, AQP7, and AQP10. In the digestive glands, especially the liver, we discuss four members of aquaporin subfamily: AQP1, AQP4, AQP5, and AQP8, three members of aquaglyceroporin subfamily: AQP7, AQP9, and AQP12. In digestive system, the abnormal expression of AQPs is closely related to the occurrence and development of a variety of diseases. AQP1 is involved in saliva secretion and fat digestion and is closely related to gastric cancer and chronic liver disease; AQP3 is involved in the diarrhea and inflammatory bowel disease; AQP4 regulates gastric acid secretion and is associated with the development of gastric cancer; AQP5 is relevant to gastric carcinoma cell proliferation and migration; AQP7 is the major aquaglyceroporin in pancreatic β cells; AQP8 plays a role in pancreatic juice secretion and may be a potential target for the treatment of diarrhea; AQP9 plays considerable role in glycerol metabolism and hepatocellular carcinoma; Studies on the function of AQP10 and AQP12 are still limited. Further studies are necessary for specific locations and functions of AQPs in digestive system.
Topics: Humans; Stomach Neoplasms; Aquaporins; Diarrhea; Liver Neoplasms; Aquaglyceroporins
PubMed: 36717492
DOI: 10.1007/978-981-19-7415-1_10 -
European Journal of Dermatology : EJD Aug 2023Aquaporins (AQPs) are a family of transmembrane channel proteins that can rapidly transport water molecules. The main subtype expressed in the epidermis and dermis is... (Review)
Review
Aquaporins (AQPs) are a family of transmembrane channel proteins that can rapidly transport water molecules. The main subtype expressed in the epidermis and dermis is AQP3. Studies have confirmed that AQPs exert certain physiological functions in the skin, such as the maintenance of normal shape, the regulation of body temperature, moisturization and hydration, anti-aging, damage repair and antigen presentation. The abnormal expression of AQPs in skin cells can lead to a variety of skin diseases. This review summarizes the relevance of AQPs in dermatophysiological and pathophysiological processes, highlighting their potential as new drug targets for the treatment of skin diseases.
Topics: Humans; Aquaporin 3; Aquaporins; Skin; Epidermis; Skin Diseases
PubMed: 37823486
DOI: 10.1684/ejd.2023.4526 -
Biochemical Society Transactions Dec 2021Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often... (Review)
Review
Pore-forming proteins (PFPs) are a broad class of molecules that comprise various families, structural folds, and assembly pathways. In nature, PFPs are most often deployed by their host organisms to defend against other organisms. In humans, this is apparent in the immune system, where several immune effectors possess pore-forming activity. Furthermore, applications of PFPs are found in next-generation low-cost DNA sequencing, agricultural crop protection, pest control, and biosensing. The advent of cryoEM has propelled the field forward. Nevertheless, significant challenges and knowledge-gaps remain. Overcoming these challenges is particularly important for the development of custom, purpose-engineered PFPs with novel or desired properties. Emerging single-molecule techniques and methods are helping to address these unanswered questions. Here we review the current challenges, problems, and approaches to studying PFPs.
Topics: Cryoelectron Microscopy; DNA; High-Throughput Nucleotide Sequencing; Humans; Porins
PubMed: 34747994
DOI: 10.1042/BST20210706 -
Nano Letters Oct 2023Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of...
Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements.
Topics: Nanopores; Nucleosides; Reproducibility of Results; Porins; Mycobacterium smegmatis
PubMed: 37818841
DOI: 10.1021/acs.nanolett.3c02872