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International Journal of Molecular... May 2020Ammonium transporter (AMT)-mediated acquisition of ammonium nitrogen from soils is essential for the nitrogen demand of plants, especially for those plants growing in... (Review)
Review
Ammonium transporter (AMT)-mediated acquisition of ammonium nitrogen from soils is essential for the nitrogen demand of plants, especially for those plants growing in flooded or acidic soils where ammonium is dominant. Recent advances show that AMTs additionally participate in many other physiological processes such as transporting ammonium from symbiotic fungi to plants, transporting ammonium from roots to shoots, transferring ammonium in leaves and reproductive organs, or facilitating resistance to plant diseases via ammonium transport. Besides being a transporter, several AMTs are required for the root development upon ammonium exposure. To avoid the adverse effects of inadequate or excessive intake of ammonium nitrogen on plant growth and development, activities of AMTs are fine-tuned not only at the transcriptional level by the participation of at least four transcription factors, but also at protein level by phosphorylation, pH, endocytosis, and heterotrimerization. Despite these progresses, it is worth noting that stronger growth inhibition, not facilitation, unfortunately occurs when AMT overexpression lines are exposed to optimal or slightly excessive ammonium. This implies that a long road remains towards overcoming potential limiting factors and achieving AMT-facilitated yield increase to accomplish the goal of persistent yield increase under the present high nitrogen input mode in agriculture.
Topics: Ammonium Compounds; Arabidopsis; Cation Transport Proteins; Gene Expression Regulation, Plant; Ion Transport; Membrane Transport Proteins; Plant Leaves; Plant Physiological Phenomena; Plant Roots; Plants
PubMed: 32443561
DOI: 10.3390/ijms21103557 -
Current Drug Metabolism 2021
Topics: Computer Simulation; Drug Discovery; Drug Interactions; Humans; Membrane Transport Proteins; Models, Biological; Pharmaceutical Preparations; Pharmacokinetics
PubMed: 34525918
DOI: 10.2174/138920022207210812124757 -
ACS Infectious Diseases Nov 2023Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One... (Review)
Review
Despite colossal achievements in antibiotic therapy in recent decades, drug-resistant pathogens have remained a leading cause of death and economic loss globally. One such WHO-critical group pathogen is . The extensive and inappropriate treatments for infections have led from multi-drug resistance (MDR) to extensive drug resistance (XDR). The synergy between efflux-mediated systems and outer membrane proteins (OMPs) may favor MDR in . Differential expression of the efflux system and OMPs (influx) and positional mutations are the factors that can be correlated to the development of drug resistance. Insights into the mechanism of influx and efflux of antibiotics can aid in developing a structurally stable molecule that can be proficient at escaping from the resistance loops in . Understanding the strategic responsibilities and developing policies to address the surge of drug resistance at the national, regional, and global levels are the needs of the hour. In this Review, we attempt to aggregate all the available research findings and delineate the resistance mechanisms by dissecting the involvement of OMPs and efflux systems. Integrating major OMPs and the efflux system's differential expression and positional mutation in may provide insight into developing strategic therapies for one health application.
Topics: Membrane Proteins; Membrane Transport Proteins; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Salmonella
PubMed: 37910638
DOI: 10.1021/acsinfecdis.3c00408 -
Current Opinion in Genetics &... Oct 2019The formation of complex multidomain proteins has occurred many times during evolution. For enzymes, this often confers the addition of new functions or new routes to... (Review)
Review
The formation of complex multidomain proteins has occurred many times during evolution. For enzymes, this often confers the addition of new functions or new routes to regulate function. Herein we review how this same process has impacted on the function of membrane transporters and channels, proteins that, due to their integral membrane location, are potentially more constrained in the fusions they can accommodate. Using examples primarily from bacterial systems, we illustrate diverse instances of functional fusions and find evidence for promiscuous fusion partners that have fused to many different classes of membrane protein. We consider the evidence that topology and stoichiometry issues might limit the range of fusions that are selected in nature and attempt to find examples where a functional benefit of direct fusion over split proteins has been demonstrated. Finally, we consider whether the reverse process of gene fission has been important in membrane transporter evolution.
Topics: Bacteria; Evolution, Molecular; Ion Channels; Membrane Proteins; Membrane Transport Proteins; Protein Domains
PubMed: 31562976
DOI: 10.1016/j.gde.2019.07.017 -
Translational Stroke Research Dec 2022
Topics: Humans; Membrane Transport Proteins; Cerebrovascular Disorders; Symporters
PubMed: 35349052
DOI: 10.1007/s12975-022-01015-6 -
Cells Apr 2022Sugars are the major source of energy in living organisms and play important roles in osmotic regulation, cell signaling and energy storage. SWEETs (Sugars Will... (Review)
Review
Sugars are the major source of energy in living organisms and play important roles in osmotic regulation, cell signaling and energy storage. SWEETs (Sugars Will Eventually be Exported Transporters) are the most recent family of sugar transporters that function as uniporters, facilitating the diffusion of sugar molecules across cell membranes. In plants, SWEETs play roles in multiple physiological processes including phloem loading, senescence, pollen nutrition, grain filling, nectar secretion, abiotic (drought, heat, cold, and salinity) and biotic stress regulation. In this review, we summarized the role of SWEET transporters in plant development and abiotic stress. The gene expression dynamics of various SWEET transporters under various abiotic stresses in different plant species are also discussed. Finally, we discuss the utilization of genome editing tools (TALENs and CRISPR/Cas9) to engineer SWEET genes that can facilitate trait improvement. Overall, recent advancements on SWEETs are highlighted, which could be used for crop trait improvement and abiotic stress tolerance.
Topics: Gene Expression Regulation, Plant; Membrane Transport Proteins; Plant Development; Plant Proteins; Plants; Stress, Physiological; Sugars
PubMed: 35455982
DOI: 10.3390/cells11081303 -
Cells Sep 2022Peptide transporter 2 (PepT2) in mammals plays essential roles in the reabsorption and conservation of peptide-bound amino acids in the kidney and in maintaining... (Review)
Review
Peptide transporter 2 (PepT2) in mammals plays essential roles in the reabsorption and conservation of peptide-bound amino acids in the kidney and in maintaining neuropeptide homeostasis in the brain. It is also of significant medical and pharmacological significance in the absorption and disposing of peptide-like drugs, including angiotensin-converting enzyme inhibitors, β-lactam antibiotics and antiviral prodrugs. Understanding the structure, function and regulation of PepT2 is of emerging interest in nutrition, medical and pharmacological research. In this review, we provide a comprehensive overview of the structure, substrate preferences and localization of PepT2 in mammals. As PepT2 is expressed in various organs, its function in the liver, kidney, brain, heart, lung and mammary gland has also been addressed. Finally, the regulatory factors that affect the expression and function of PepT2, such as transcriptional activation and posttranslational modification, are also discussed.
Topics: Amino Acids; Angiotensin-Converting Enzyme Inhibitors; Animals; Anti-Bacterial Agents; Antiviral Agents; Biology; Mammals; Membrane Transport Proteins; Peptides; Prodrugs; Symporters; beta-Lactams
PubMed: 36139448
DOI: 10.3390/cells11182874 -
Nature May 2024Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a...
Choline is an essential nutrient that the human body needs in vast quantities for cell membrane synthesis, epigenetic modification and neurotransmission. The brain has a particularly high demand for choline, but how it enters the brain remains unknown. The major facilitator superfamily transporter FLVCR1 (also known as MFSD7B or SLC49A1) was recently determined to be a choline transporter but is not highly expressed at the blood-brain barrier, whereas the related protein FLVCR2 (also known as MFSD7C or SLC49A2) is expressed in endothelial cells at the blood-brain barrier. Previous studies have shown that mutations in human Flvcr2 cause cerebral vascular abnormalities, hydrocephalus and embryonic lethality, but the physiological role of FLVCR2 is unknown. Here we demonstrate both in vivo and in vitro that FLVCR2 is a BBB choline transporter and is responsible for the majority of choline uptake into the brain. We also determine the structures of choline-bound FLVCR2 in both inward-facing and outward-facing states using cryo-electron microscopy. These results reveal how the brain obtains choline and provide molecular-level insights into how FLVCR2 binds choline in an aromatic cage and mediates its uptake. Our work could provide a novel framework for the targeted delivery of therapeutic agents into the brain.
Topics: Animals; Female; Humans; Male; Mice; Middle Aged; Biological Transport; Blood-Brain Barrier; Brain; Choline; Cryoelectron Microscopy; In Vitro Techniques; Membrane Transport Proteins; Models, Molecular
PubMed: 38693257
DOI: 10.1038/s41586-024-07326-y -
Trends in Pharmacological Sciences May 2022Solute carrier transporters (SLCs) limit receptor activation via uptake of extracellular ligands. Novel concepts are emerging that describe the modulation of...
Solute carrier transporters (SLCs) limit receptor activation via uptake of extracellular ligands. Novel concepts are emerging that describe the modulation of intracellular and plasma membrane receptors by ligand influx and efflux via SLCs, respectively. Here, we evaluate recent insights and provide an outlook for developing potential therapeutic strategies.
Topics: Biological Transport; Cell Membrane; Humans; Ligands; Membrane Transport Proteins; Solute Carrier Proteins
PubMed: 35232590
DOI: 10.1016/j.tips.2022.02.004 -
Plant Cell Reports Jan 2021This review summarizes the recent updates in the area of transporters of plant secondary metabolites, including their applied aspects in metabolic engineering of... (Review)
Review
This review summarizes the recent updates in the area of transporters of plant secondary metabolites, including their applied aspects in metabolic engineering of economically important secondary metabolites. Plants have evolved biosynthetic pathways to produce structurally diverse secondary metabolites, which serve distinct functions, including defense against pathogens and herbivory, thereby playing a pivotal role in plant ecological interactions. These compounds often display interesting bioactivities and, therefore, have been used as repositories of natural drugs and phytoceuticals for humans. At an elevated level, plant secondary metabolites could be cytotoxic to the plant cell itself; therefore, plants have developed sophisticated mechanisms to sequester these compounds to prevent cytotoxicity. Many of these valuable natural compounds and their precursors are biosynthesized and accumulated at diverse subcellular locations, and few are even transported to sink organs via long-distance transport, implying the involvement of compartmentalization via intra- and intercellular transport mechanisms. The transporter proteins belonging to different families of transporters, especially ATP binding cassette (ABC) and multidrug and toxic compound extrusion (MATE) have been implicated in membrane-mediated transport of certain plant secondary metabolites. Despite increasing reports on the characterization of transporter proteins and their genes, our knowledge about the transporters of several medicinally and economically important plant secondary metabolites is still enigmatic. A comprehensive understanding of the molecular mechanisms underlying the whole route of secondary metabolite transportome, in addition to the biosynthetic pathways, will aid in systematic and targeted metabolic engineering of high-value secondary metabolites. The present review embodies a comprehensive update on the progress made in the elucidation of transporters of secondary metabolites in view of basic and applied aspects of their transport mechanism.
Topics: ATP-Binding Cassette Transporters; Alkaloids; Biological Transport; Membrane Transport Proteins; Metabolic Engineering; Plant Proteins; Plants; Plants, Genetically Modified; Secondary Metabolism; Terpenes
PubMed: 32959124
DOI: 10.1007/s00299-020-02599-9