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Nature Methods Dec 2020Data-independent acquisition modes isolate and concurrently fragment populations of different precursors by cycling through segments of a predefined precursor m/z range....
Data-independent acquisition modes isolate and concurrently fragment populations of different precursors by cycling through segments of a predefined precursor m/z range. Although these selection windows collectively cover the entire m/z range, overall, only a few per cent of all incoming ions are isolated for mass analysis. Here, we make use of the correlation of molecular weight and ion mobility in a trapped ion mobility device (timsTOF Pro) to devise a scan mode that samples up to 100% of the peptide precursor ion current in m/z and mobility windows. We extend an established targeted data extraction workflow by inclusion of the ion mobility dimension for both signal extraction and scoring and thereby increase the specificity for precursor identification. Data acquired from whole proteome digests and mixed organism samples demonstrate deep proteome coverage and a high degree of reproducibility as well as quantitative accuracy, even from 10 ng sample amounts.
Topics: Cell Line, Tumor; Data Science; HeLa Cells; High-Throughput Screening Assays; Humans; Ion Channels; Ion Transport; Ions; Proteome; Proteomics; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 33257825
DOI: 10.1038/s41592-020-00998-0 -
Reviews of Physiology, Biochemistry and... 2022Neoplastic transformation is associated with alterations of the ion transports across plasma and intracellular membranes. These alterations are crucial elements of the... (Review)
Review
Neoplastic transformation is associated with alterations of the ion transports across plasma and intracellular membranes. These alterations are crucial elements of the phenotypical reprogramming of the transformed cells and may promote adaptation to hypoxia, malignant progression, tumor spreading and metastasis, as well as therapy resistance. The present review article focuses on ion transport processes in tumor cells that are induced by ionizing radiation and that contribute to radioresistance and therapy failure. In particular, this article introduces radiogenic ion transports across plasma and mitochondrial membranes and discusses their functional significance for cell cycle control, DNA repair, accelerated repopulation, cell migration and metastasis, metabolic reprogramming, adaptation to hypoxia, and radiogenic formation of reactive oxygen species.
Topics: DNA Repair; Humans; Hypoxia; Ion Transport; Neoplasms; Radiation, Ionizing
PubMed: 32737751
DOI: 10.1007/112_2020_33 -
International Journal of Molecular... Jan 2022The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion... (Review)
Review
The TMEM16A/anoctamin-1 calcium-activated chloride channel (CaCC) contributes to a range of vital functions, such as the control of vascular tone and epithelial ion transport. The channel is a founding member of a family of 10 proteins (TMEM16x) with varied functions; some members (i.e., TMEM16A and TMEM16B) serve as CaCCs, while others are lipid scramblases, combine channel and scramblase function, or perform additional cellular roles. TMEM16x proteins are typically activated by agonist-induced Ca release evoked by G-protein-coupled receptor (GPCR) activation; thus, TMEM16x proteins link Ca-signalling with cell electrical activity and/or lipid transport. Recent studies demonstrate that a range of other cellular factors-including plasmalemmal lipids, pH, hypoxia, ATP and auxiliary proteins-also control the activity of the TMEM16A channel and its paralogues, suggesting that the TMEM16x proteins are effectively polymodal sensors of cellular homeostasis. Here, we review the molecular pathophysiology, structural biology, and mechanisms of regulation of TMEM16x proteins by multiple cellular factors.
Topics: Animals; Anoctamin-1; Anoctamins; Biological Transport; Cell Membrane; Chloride Channels; Humans; Ion Transport; Phospholipid Transfer Proteins
PubMed: 35163502
DOI: 10.3390/ijms23031580 -
Journal of Cystic Fibrosis : Official... Mar 2020Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF... (Review)
Review
Mutations associated with cystic fibrosis (CF) have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common CF mutation, F508del, disrupts the processing to and stability at the plasma membrane and function as a Cl channel. CFTR is surrounded by a dynamic network of interacting components, referred to as the CFTR Functional Landscape, that impact its synthesis, folding, stability, trafficking and function. CFTR interacting proteins can be manipulated by functional genomic approaches to rescue the trafficking and functional defects characteristic of CF. Here we review recent efforts to elucidate the impact of genetic variation on the ability of the nascent CFTR polypeptide to interact with the proteostatic environment. We also provide an overview of how specific components of this protein network can be modulated to rescue the trafficking and functional defects associated with the F508del variant of CFTR. The identification of novel proteins playing key roles in the processing of CFTR could pave the way for their use as novel therapeutic targets to provide synergistic correction of mutant CFTR for the greater benefit of individuals with CF.
Topics: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Therapy; Humans; Ion Transport; Membrane Transport Modulators; Mutation; Proteostasis
PubMed: 31680043
DOI: 10.1016/j.jcf.2019.10.017 -
The New Phytologist Jan 2021The coordinated control of ion transport across the two major membranes of differentiated plant cells, the plasma and the vacuolar membranes, is fundamental in cell... (Review)
Review
The coordinated control of ion transport across the two major membranes of differentiated plant cells, the plasma and the vacuolar membranes, is fundamental in cell physiology. The stomata responses to the fluctuating environmental conditions are an illustrative example. Indeed, they rely on the coordination of ion fluxes between the different cell compartments. The cytosolic environment, which is an interface between intracellular compartments, and the activity of the ion transporters localised in the different membranes influence one each other. Here we analyse the molecular mechanisms connecting and modulating the transport processes at both the plasma and the vacuolar membranes of guard cells.
Topics: Arabidopsis; Biological Transport; Cell Membrane; Ion Transport; Vacuoles
PubMed: 33007120
DOI: 10.1111/nph.16983 -
Chemical Society Reviews Sep 2023Bio-markers, such as ions, small molecules, nucleic acids, peptides, proteins and cells, participate in the construction of living organisms and play important roles in... (Review)
Review
Bio-markers, such as ions, small molecules, nucleic acids, peptides, proteins and cells, participate in the construction of living organisms and play important roles in biological processes. It is of great significance to accurately detect these bio-markers for studying their basic functions, the development of molecular diagnosis and to better understand life processes. Solid-state nanochannel-based sensing systems have been demonstrated for the detection of bio-markers, due to their rapid, label-free and high-throughput screening, with high sensitivity and specificity. Generally, studies on solid-state nanochannels have focused on probes on the inner-wall (PIW), ignoring probes on the outer-surface (POS). As a result, the direct detection of cells is difficult to realize by these inner-wall focused nanochannels. Moreover, the sensitivity for detecting ions, small molecules, nucleic acids, peptides and proteins requires further improvement. Recent research has focused on artificial solid-state nanochannels with POS, which have demonstrated the ability to independently regulate ion transport. This design not only contributes to the detection of large analytes, such as cells, but also provides promising opportunities for ultra-high sensitivity detection with a clear mechanism. In this tutorial review, we present an overview of the detection principle used for solid-state nanochannels, inner-wall focused nanochannels and outer-surface focused nanochannels. Furthermore, we discuss the remaining challenges faced by current nanochannel technologies and provide insights into their prospects.
Topics: Nanostructures; Ion Transport; Nucleic Acids; Peptides; Ions
PubMed: 37581902
DOI: 10.1039/d2cs00865c -
Annual Review of Analytical Chemistry... 2015Iontronics is an emerging technology based on sophisticated control of ions as signal carriers that bridges solid-state electronics and biological system. It is found in... (Review)
Review
Iontronics is an emerging technology based on sophisticated control of ions as signal carriers that bridges solid-state electronics and biological system. It is found in nature, e.g., information transduction and processing of brain in which neurons are dynamically polarized or depolarized by ion transport across cell membranes. It suggests the operating principle of aqueous circuits made of predesigned structures and functional materials that characteristically interact with ions of various charge, mobility, and affinity. Working in aqueous environments, iontronic devices offer profound implications for biocompatible or biodegradable logic circuits for sensing, ecofriendly monitoring, and brain-machine interfacing. Furthermore, iontronics based on multi-ionic carriers sheds light on futuristic biomimic information processing. In this review, we overview the historical achievements and the current state of iontronics with regard to theory, fabrication, integration, and applications, concluding with comments on where the technology may advance.
Topics: Animals; Electronics; Humans; Ion Transport; Ions
PubMed: 26048549
DOI: 10.1146/annurev-anchem-071114-040202 -
Neuron Sep 2015Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of... (Review)
Review
Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.
Topics: Animals; Humans; Ion Channel Gating; Ion Channels; Ion Transport; Mechanotransduction, Cellular; Sensation; Touch
PubMed: 26402601
DOI: 10.1016/j.neuron.2015.08.032 -
Journal of Molecular Biology Jan 2015Ion channels facilitate the passive movement of ions down an electrochemical gradient and across lipid bilayers in cells. This phenomenon is essential for life and... (Review)
Review
Ion channels facilitate the passive movement of ions down an electrochemical gradient and across lipid bilayers in cells. This phenomenon is essential for life and underlies many critical homeostatic processes in cells. Ion channels are diverse and differ with respect to how they open and close (gating) and to their ionic conductance/selectivity (permeation). Fundamental understanding of ion channel structure-function mechanisms, their physiological roles, how their dysfunction leads to disease, their utility as biosensors, and development of novel molecules to modulate their activity are important and active research frontiers. In this review, we focus on ion channel engineering approaches that have been applied to investigate these aspects of ion channel function, with a major emphasis on voltage-gated ion channels.
Topics: Animals; Humans; Ion Channels; Ion Transport; Protein Engineering
PubMed: 25205552
DOI: 10.1016/j.jmb.2014.09.001 -
Organic & Biomolecular Chemistry Jul 2023The pH regulation of transmembrane ion transport is critical for biological processes and has a direct implication on diseases such as cancer. Synthetic transporters... (Review)
Review
The pH regulation of transmembrane ion transport is critical for biological processes and has a direct implication on diseases such as cancer. Synthetic transporters that can be regulated using pH show promise as therapeutic agents. This review highlights the importance of the fundamental principles of acid-base chemistry in achieving pH regulation. A systematic classification of transporters based on the p of their pH-responsive units aids in correlating the pH regulation of ion transport with the molecular structure. This review also summarises the applications of these transporters and their efficacy in cancer therapy.
Topics: Humans; Hydrogen-Ion Concentration; Ion Transport; Homeostasis; Neoplasms; Molecular Structure
PubMed: 37404004
DOI: 10.1039/d3ob00496a