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Current Biology : CB Apr 2024In this Quick guide, Palmer and Berks introduce the twin-arginine translocation (Tat) systems. Tats are found in a variety of microbes and microbe-derived organelles,...
In this Quick guide, Palmer and Berks introduce the twin-arginine translocation (Tat) systems. Tats are found in a variety of microbes and microbe-derived organelles, and are known to translocate folded substrate proteins across biological membranes.
Topics: Membrane Transport Proteins; Escherichia coli Proteins; Twin-Arginine-Translocation System; Cell Membrane; Arginine; Protein Transport; Protein Sorting Signals; Bacterial Proteins
PubMed: 38593766
DOI: 10.1016/j.cub.2024.02.039 -
International Journal of Molecular... Jan 2021This editorial summarizes the 13 scientific papers published in the Special Issue "Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations" of the...
This editorial summarizes the 13 scientific papers published in the Special Issue "Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations" of the [...].
Topics: Cations; Chemical Phenomena; Drug Discovery; Membrane Transport Proteins
PubMed: 33450934
DOI: 10.3390/ijms22020732 -
Neuropharmacology Dec 2019ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved... (Review)
Review
ɣ-aminobutyric-acid (GABA) functions as the principal inhibitory neurotransmitter in the central nervous system. Imbalances in GABAergic neurotransmission are involved in the pathophysiology of various neurological diseases such as epilepsy, Alzheimer's disease and stroke. GABA transporters (GATs) facilitate the termination of GABAergic signaling by transporting GABA together with sodium and chloride from the synaptic cleft into presynaptic neurons and surrounding glial cells. Four different GATs have been identified that all belong to the solute carrier 6 (SLC6) transporter family: GAT1-3 (SLC6A1, SLC6A13, SLC6A11) and betaine/GABA transporter 1 (BGT1, SLC6A12). BGT1 has emerged as an interesting target for treating epilepsy due to animal studies that reported anticonvulsant effects for the GAT1/BGT1 selective inhibitor EF1502 and the BGT1 selective inhibitor RPC-425. However, the precise involvement of BGT1 in epilepsy remains elusive because of its controversial expression levels in the brain and the lack of highly selective and potent tool compounds. This review gathers the current structural and functional knowledge on BGT1 with emphasis on brain relevance, discusses all available compounds, and tries to shed light on the molecular determinants driving BGT1 selectivity. This article is part of the issue entitled 'Special Issue on Neurotransmitter Transporters'.
Topics: Animals; Brain; GABA Plasma Membrane Transport Proteins; Humans
PubMed: 31108110
DOI: 10.1016/j.neuropharm.2019.05.021 -
Current Opinion in Plant Biology Aug 2022The nitrate and peptide transporter family (NPF) is one of the largest transporter families in the plant kingdom. The name of the family reflects the substrates (nitrate... (Review)
Review
The nitrate and peptide transporter family (NPF) is one of the largest transporter families in the plant kingdom. The name of the family reflects the substrates (nitrate and peptides) identified for the two founding members CHL1 and PTR2 from Arabidopsis thaliana almost 30 years ago. However, since then, the NPF has emerged as a hotspot for transporters with a wide range of crucial roles in plant specialized metabolism. Recent prominent examples include 1) controlling accumulation of antinutritional glucosinolates in Brassica seeds, 2) deposition of heat-stress tolerance flavonol diglucosides to pollen coats 3) production of anti-cancerous monoterpene indole alkaloid precursors in Catharanthus roseus and 4) detoxification of steroid glycoalkaloids in ripening tomatoes. In this review, we turn the spotlight on the emerging role of the NPF in plant specialized metabolism and its potential for improving crop traits through transport engineering.
Topics: Anion Transport Proteins; Arabidopsis; Gene Expression Regulation, Plant; Membrane Transport Proteins; Nitrates; Peptides; Plant Proteins; Plants
PubMed: 35709542
DOI: 10.1016/j.pbi.2022.102243 -
Science China. Life Sciences Nov 2023Iron (Fe) is an essential micronutrient for all organisms. Fe availability in the soil is usually much lower than that required for plant growth, and Fe deficiencies...
Iron (Fe) is an essential micronutrient for all organisms. Fe availability in the soil is usually much lower than that required for plant growth, and Fe deficiencies seriously restrict crop growth and yield. Calcium (Ca) is a second messenger in all eukaryotes; however, it remains largely unknown how Ca regulates Fe deficiency. In this study, mutations in CPK21 and CPK23, which are two highly homologous calcium-dependent protein kinases, conferredimpaired growth and rootdevelopment under Fe-deficient conditions, whereas constitutively active CPK21 and CPK23 enhanced plant tolerance to Fe-deficient conditions. Furthermore, we found that CPK21 and CPK23 interacted with and phosphorylated the Fe transporter IRON-REGULATED TRANSPORTER1 (IRT1) at the Ser149 residue. Biochemical analyses and complementation of Fe transport in yeast and plants indicated that IRT1 Ser149 is critical for IRT1 transport activity. Taken together, these findings suggest that the CPK21/23-IRT1 signaling pathway is critical for Fe homeostasis in plants and provides targets for improving Fe-deficient environments and breeding crops resistant to Fe-deficient conditions.
Topics: Arabidopsis; Arabidopsis Proteins; Calcium; Plant Breeding; Membrane Transport Proteins; Protein Kinases; Iron Deficiencies; Gene Expression Regulation, Plant; Plant Roots; Cation Transport Proteins
PubMed: 37286859
DOI: 10.1007/s11427-022-2330-4 -
Molecular and Cellular Endocrinology Mar 2020The Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) domain is a ~210 amino acid sequence that folds into an α/β helix-grip structure forming a... (Review)
Review
The Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) domain is a ~210 amino acid sequence that folds into an α/β helix-grip structure forming a hydrophobic pocket for lipid binding. The helix-grip fold structure defines a large superfamily of proteins, and this review focuses on the mammalian START domain family members that include single START domain proteins with identified ligands, and larger multi-domain proteins that may have novel roles in metabolism. Much of our understanding of the mammalian START domain proteins in lipid transport and changes in metabolism has advanced through studies using knockout mouse models, although for some of these proteins the identity and/or physiological role of ligand binding remains unknown. The findings that helped define START domain lipid-binding specificity, lipid transport, and changes in metabolism are presented to highlight that fundamental questions remain regarding the biological function(s) for START domain-containing proteins.
Topics: Animals; Biological Transport; Carrier Proteins; Humans; Intracellular Space; Lipid Metabolism; Membrane Transport Proteins; Mice; Mice, Knockout; Phosphoproteins
PubMed: 31927098
DOI: 10.1016/j.mce.2020.110704 -
Biomolecules May 2021The notion of mitochondria being involved in the decoding and shaping of intracellular Ca signals has been circulating since the end of the 19th century. Despite that,... (Review)
Review
The notion of mitochondria being involved in the decoding and shaping of intracellular Ca signals has been circulating since the end of the 19th century. Despite that, the molecular identity of the channel that mediates Ca ion transport into mitochondria remained elusive for several years. Only in the last decade, the genes and pathways responsible for the mitochondrial uptake of Ca began to be cloned and characterized. The gene coding for the pore-forming unit of the mitochondrial channel was discovered exactly 10 years ago, and its product was called mitochondrial Ca uniporter or MCU. Before that, only one of its regulators, the mitochondria Ca uptake regulator 1, MICU1, has been described in 2010. However, in the following years, the scientific interest in mitochondrial Ca signaling regulation and physiological role has increased. This shortly led to the identification of many of its components, to the description of their 3D structure, and the characterization of the uniporter contribution to tissue physiology and pathology. In this review, we will summarize the most relevant achievements in the history of mitochondrial Ca studies, presenting a chronological overview of the most relevant and landmarking discoveries. Finally, we will explore the impact of mitochondrial Ca signaling in the context of muscle physiology, highlighting the recent advances in understanding the role of the MCU complex in the control of muscle trophism and metabolism.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Calcium-Binding Proteins; Cation Transport Proteins; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Ion Transport; Mitochondria; Mitochondrial Membrane Transport Proteins
PubMed: 34071006
DOI: 10.3390/biom11060786 -
Biotechnology Letters Jun 2021Cytidine is an important raw material for nucleic acid health food and genetic engineering research. In recent years, it has shown irreplaceable effects in anti-virus,...
Cytidine is an important raw material for nucleic acid health food and genetic engineering research. In recent years, it has shown irreplaceable effects in anti-virus, anti-tumor, and AIDS drugs. Its biosynthetic pathway is complex and highly regulated. In this study, overexpression of uracil permease and a nucleoside transporter from Bacillus amyloliquefaciens related to cell membrane transport in Escherichia coli strain BG-08 was found to increase cytidine production in shake flask cultivation by 1.3-fold (0.91 ± 0.03 g/L) and 1.8-fold (1.26 ± 0.03 g/L) relative to that of the original strain (0.70 ± 0.03 g/L), respectively. Co-overexpression of uracil permease and a nucleoside transporter further increased cytidine yield by 2.7-fold (1.59 ± 0.05 g/L) compared with that of the original strain. These results indicate that the overexpressed uracil permease and nucleoside transporter can promote the accumulation of cytidine, and the two proteins play a synergistic role in the secretion of cytidine in Escherichia coli.
Topics: Bacillus amyloliquefaciens; Bacterial Proteins; Bacteriological Techniques; Batch Cell Culture Techniques; Biosynthetic Pathways; Cytidine; Escherichia coli; Membrane Transport Proteins; Nucleoside Transport Proteins; Protein Engineering
PubMed: 33646457
DOI: 10.1007/s10529-021-03103-3 -
Plant Physiology Dec 2021Sucrose, hexoses, and raffinose play key roles in the plant metabolism. Sucrose and raffinose, produced by photosynthesis, are translocated from leaves to flowers,... (Review)
Review
Sucrose, hexoses, and raffinose play key roles in the plant metabolism. Sucrose and raffinose, produced by photosynthesis, are translocated from leaves to flowers, developing seeds and roots. Translocation occurs in the sieve elements or sieve tubes of angiosperms. But how is sucrose loaded into and unloaded from the sieve elements? There seem to be two principal routes: one through plasmodesmata and one via the apoplasm. The best-studied transporters are the H+/SUCROSE TRANSPORTERs (SUTs) in the sieve element-companion cell complex. Sucrose is delivered to SUTs by SWEET sugar uniporters that release these key metabolites into the apoplasmic space. The H+/amino acid permeases and the UmamiT amino acid transporters are hypothesized to play analogous roles as the SUT-SWEET pair to transport amino acids. SWEETs and UmamiTs also act in many other important processes-for example, seed filling, nectar secretion, and pollen nutrition. We present information on cell type-specific enrichment of SWEET and UmamiT family members and propose several members to play redundant roles in the efflux of sucrose and amino acids across different cell types in the leaf. Pathogens hijack SWEETs and thus represent a major susceptibility of the plant. Here, we provide an update on the status of research on intercellular and long-distance translocation of key metabolites such as sucrose and amino acids, communication of the plants with the root microbiota via root exudates, discuss the existence of transporters for other important metabolites and provide potential perspectives that may direct future research activities.
Topics: Amino Acids; Biological Transport; Membrane Transport Proteins; Phloem; Plasmodesmata; Sugars
PubMed: 34015139
DOI: 10.1093/plphys/kiab228 -
Frontiers in Immunology 2020Timely and precise delivery of the endosomal Toll-like receptors (TLRs) to the ligand recognition site is a critical event in mounting an effective antimicrobial immune... (Review)
Review
Timely and precise delivery of the endosomal Toll-like receptors (TLRs) to the ligand recognition site is a critical event in mounting an effective antimicrobial immune response, however, the same TLRs should maintain the delicate balance of avoiding recognition of self-nucleic acids. Such sensing is widely known to start from endosomal compartments, but recently enough evidence has accumulated supporting the idea that TLR-mediated signaling pathways originating in the cell membrane may be engaged in various cells due to differential expression and distribution of the endosomal TLRs. Therefore, the presence of endosomal TLRs on the cell surface could benefit the host responses in certain cell types and/or organs. Although not fully understood why, TLR3, TLR7, and TLR9 may occur both in the cell membrane and intracellularly, and it seems that activation of the immune response can be initiated concurrently from these two sites in the cell. Furthermore, various forms of endosomal TLRs may be transported to the cell membrane, indicating that this may be a normal process orchestrated by cysteine proteases-cathepsins. Among the endosomal TLRs, TLR3 belongs to the evolutionary distinct group and engages a different protein adapter in the signaling cascade. The differently glycosylated forms of TLR3 are transported by UNC93B1 to the cell membrane, unlike TLR7, TLR8, and TLR9. The aim of this review is to reconcile various views on the cell surface positioning of endosomal TLRs and add perspective to the implication of such receptor localization on their function, with special attention to TLR3. Cell membrane-localized TLR3, TLR7, and TLR9 may contribute to endosomal TLR-mediated inflammatory signaling pathways. Dissecting this signaling axis may serve to better understand mechanisms influencing endosomal TLR-mediated inflammation, thus determine whether it is a necessity for immune response or simply a circumstantial superfluous duplication, with other consequences on immune response.
Topics: Animals; Cathepsins; Cell Membrane; Endosomes; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen-Ion Concentration; Inflammation; Ligands; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Nucleic Acids; Protein Binding; Signal Transduction; Toll-Like Receptors
PubMed: 33597952
DOI: 10.3389/fimmu.2020.620972