0
selected
-
1.
Mass Spectrometry of Human Transporters.
Achour, B, Al-Majdoub, ZM, Rostami-Hodjegan, A, Barber, J
Annual review of analytical chemistry (Palo Alto, Calif.). 2020;(1):223-247
Abstract
Transporters are key to understanding how an individual will respond to a particular dose of a drug. Two patients with similar systemic concentrations may have quite different local concentrations of a drug at the required site. The transporter profile of any individual depends upon a variety of genetic and environmental factors, including genotype, age, and diet status. Robust models (virtual patients) are therefore required and these models are data hungry. Necessary data include quantitative transporter profiles at the relevant organ. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is currently the most powerful method available for obtaining this information. Challenges include sourcing the tissue, isolating the hydrophobic membrane-embedded transporter proteins, preparing the samples for MS (including proteolytic digestion), choosing appropriate quantification methodology, and optimizing the LC-MS/MS conditions. Great progress has been made with all of these, especially within the last few years, and is discussed here.
-
2.
Regulation of nutrient transporters by metabolic and environmental stresses.
Babst, M
Current opinion in cell biology. 2020;:35-41
-
-
Free full text
-
Abstract
The yeast plasma membrane is a selective barrier between an erratic environment and the cell's metabolism. Nutrient transporters are the gatekeepers that control the import of molecules feeding into the metabolic pathways. Nutrient import adjusts rapidly to changes in metabolism and the environment, which is accomplished by regulating the surface expression of transporters. Recent studies indicate that the lipid environment in which transporters function regulates ubiquitination efficiency and endocytosis of these proteins. Changes in the lipid environment are caused by lateral movements of the transporters between different membrane domains and by the influence of the extracellular environment on the fluidity of the plasma membrane.
-
3.
Membrane Transporters for Amino Acids as Players of Cancer Metabolic Rewiring.
Scalise, M, Console, L, Rovella, F, Galluccio, M, Pochini, L, Indiveri, C
Cells. 2020;(9)
Abstract
Cancer cells perform a metabolic rewiring to sustain an increased growth rate and compensate for the redox stress caused by augmented energy metabolism. The metabolic changes are not the same in all cancers. Some features, however, are considered hallmarks of this disease. As an example, all cancer cells rewire the amino acid metabolism for fulfilling both the energy demand and the changed signaling routes. In these altered conditions, some amino acids are more frequently used than others. In any case, the prerequisite for amino acid utilization is the presence of specific transporters in the cell membrane that can guarantee the absorption and the traffic of amino acids among tissues. Tumor cells preferentially use some of these transporters for satisfying their needs. The evidence for this phenomenon is the over-expression of selected transporters, associated with specific cancer types. The knowledge of the link between the over-expression and the metabolic rewiring is crucial for understanding the molecular mechanism of reprogramming in cancer cells. The continuous growth of information on structure-function relationships and the regulation of transporters will open novel perspectives in the fight against human cancers.
-
4.
Proteomic and Bioinformatic Profiling of Transporters in Higher Plant Mitochondria.
Møller, IM, Rao, RSP, Jiang, Y, Thelen, JJ, Xu, D
Biomolecules. 2020;(8)
Abstract
To function as a metabolic hub, plant mitochondria have to exchange a wide variety of metabolic intermediates as well as inorganic ions with the cytosol. As identified by proteomic profiling or as predicted by MU-LOC, a newly developed bioinformatics tool, Arabidopsis thaliana mitochondria contain 128 or 143 different transporters, respectively. The largest group is the mitochondrial carrier family, which consists of symporters and antiporters catalyzing secondary active transport of organic acids, amino acids, and nucleotides across the inner mitochondrial membrane. An impressive 97% (58 out of 60) of all the known mitochondrial carrier family members in Arabidopsis have been experimentally identified in isolated mitochondria. In addition to many other secondary transporters, Arabidopsis mitochondria contain the ATP synthase transporters, the mitochondria protein translocase complexes (responsible for protein uptake across the outer and inner membrane), ATP-binding cassette (ABC) transporters, and a number of transporters and channels responsible for allowing water and inorganic ions to move across the inner membrane driven by their transmembrane electrochemical gradient. A few mitochondrial transporters are tissue-specific, development-specific, or stress-response specific, but this is a relatively unexplored area in proteomics that merits much more attention.
-
5.
The oligopeptide ABC-importers are essential communication channels in Gram-positive bacteria.
Slamti, L, Lereclus, D
Research in microbiology. 2019;(8):338-344
Abstract
The transport of peptides in microorganisms plays an important role in their physiology and behavior, both as a nutrient source and as a proxy to sense their environment. This latter function is evidenced in Gram-positive bacteria where cell-cell communication is mediated by small peptides. Here, we highlight the importance of the oligopeptide permease (Opp) systems in the various major processes controlled by signaling peptides, such as sporulation, virulence and conjugation. We underline that the functioning of these communication systems is tightly linked to the developmental status of the bacteria via the regulation of opp gene expression by transition phase regulators.
-
6.
Dissecting the Proton Transport Pathway in Oral Squamous Cell Carcinoma: State of the Art and Theranostics Implications.
Lorenzo-Pouso, AI, Pérez-Sayáns, M, Rodríguez-Zorrilla, S, Chamorro-Petronacci, C, García-García, A
International journal of molecular sciences. 2019;(17)
Abstract
Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCC.
-
7.
[Thiamine-responsive megaloblastic anemia or Rogers syndrome: A literature review].
Lu, H, Lu, H, Vaucher, J, Tran, C, Vollenweider, P, Castioni, J
La Revue de medecine interne. 2019;(1):20-27
Abstract
Thiamine-responsive megaloblastic anemia (TRMA), also known as Rogers syndrome, is a rare autosomal recessive disease characterized by three main components: megaloblastic anemia, diabetes mellitus and sensorineural deafness. Those features occur in infancy but may arise during adolescence. Diagnosis relies on uncovering genetic variations (alleles) in the SLC19A2 gene, encoding for a high affinity thiamine transporter. This transporter is essentially present in hematopoietic stem cells, pancreatic beta cells and inner ear cells, explaining the clinical manifestations of the disease. Based on a multidisciplinary approach, treatment resides on lifelong thiamine oral supplementation at pharmacological doses, which reverses anemia and may delay development of diabetes. However, thiamine supplementation does not alleviate already existing hearing defects.
-
8.
PIN-FORMED and PIN-LIKES auxin transport facilitators.
Sauer, M, Kleine-Vehn, J
Development (Cambridge, England). 2019;(15)
Abstract
The phytohormone auxin influences virtually all aspects of plant growth and development. Auxin transport across membranes is facilitated by, among other proteins, members of the PIN-FORMED (PIN) and the structurally similar PIN-LIKES (PILS) families, which together govern directional cell-to-cell transport and intracellular accumulation of auxin. Canonical PIN proteins, which exhibit a polar localization in the plasma membrane, determine many patterning and directional growth responses. Conversely, the less-studied non-canonical PINs and PILS proteins, which mostly localize to the endoplasmic reticulum, attenuate cellular auxin responses. Here, and in the accompanying poster, we provide a brief summary of current knowledge of the structure, evolution, function and regulation of these auxin transport facilitators.
-
9.
Intracellular phosphate homeostasis - A short way from metabolism to signaling.
Fabiańska, I, Bucher, M, Häusler, RE
Plant science : an international journal of experimental plant biology. 2019;:57-67
Abstract
Phosphorus in plant cells occurs in inorganic form as both ortho- and pyrophosphate or bound to organic compounds, like e.g., nucleotides, phosphorylated metabolites, phospholipids, phosphorylated proteins, or phytate as P storage in the vacuoles of seeds. Individual compartments of the cell are surrounded by membranes that are selective barriers to avoid uncontrolled solute exchange. A controlled exchange of phosphate or phosphorylated metabolites is accomplished by specific phosphate transporters (PHTs) and the plastidial phosphate translocator family (PTs) of the inner envelope membrane. Plastids, in particular chloroplasts, are the site of various anabolic sequences of enzyme-catalyzed reactions. Apart from their role in metabolism PHTs and PTs are presumed to be also involved in communication between organelles and plant organs. Here we will focus on the integration of phosphate transport and homeostasis in signaling processes. Recent developments in this field will be critically assessed and potential future developments discussed. In particular, the occurrence of various plastid types in one organ (i.e. the leaf) with different functions with respect to metabolism or sensing, as has been documented recently following a tissue-specific proteomics approach (Beltran et al., 2018), will shed new light on functional aspects of phosphate homeostasis.
-
10.
A Delicate Connection: c-di-AMP Affects Cell Integrity by Controlling Osmolyte Transport.
Commichau, FM, Gibhardt, J, Halbedel, S, Gundlach, J, Stülke, J
Trends in microbiology. 2018;(3):175-185
Abstract
Bacteria use second-messenger molecules to adapt to their environment. Several second messengers, among them cyclic di-AMP (c-di-AMP), have been discovered and intensively studied. Interestingly, c-di-AMP is essential for growth of Gram-positive bacteria such as Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus. Many studies demonstrated that perturbation of c-di-AMP metabolism affects the integrity of the bacterial cell envelope. Therefore, it has been assumed that the nucleotide is essential for proper cell envelope synthesis. In this Opinion paper, we propose that the cell envelope phenotypes caused by perturbations of c-di-AMP metabolism can be interpreted differently: c-di-AMP might indirectly control cell envelope integrity by modulating the turgor, a physical variable that needs to be tightly adjusted. We also discuss open questions related to c-di-AMP metabolism that need to be urgently addressed by future studies.