Isoform-specific N-linked glycosylation of NaV channel α-subunits alters β-subunit binding sites.

Voltage-gated sodium channel α-subunits (NaV1.1-1.9) initiate and propagate action potentials in neurons and myocytes.

Is the voltage-gated sodium channel β3 subunit (SCN3B) a biomarker for glioma?

Recent studies suggest a need for reliable biomarkers enhancing prognosis prediction and treatment strategies in cancer. Here, we performed a data analysis bearing on the expression of SCN3B, voltage-gated sodium channel (VGSC) β3 subunit, as a possible candidate for the development of a glioma biomarker for the first time. This extends our previous review article that mentioned the potential of SCN3B as a prognostic biomarker for glioma survival, further examining its association with existing indicators and immune responses.

Voltage-gated sodium channels in cancers.

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from "non-excitable" tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers.

A novel Na1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis.

Solid tumours have abnormally high intracellular [Na]. The activity of various Na channels may underlie this Na accumulation. Voltage-gated Na channels (VGSCs) have been shown to be functionally active in cancer cell lines, where they promote invasion.

Cardiac arrhythmogenesis: roles of ion channels and their functional modification.

Cardiac arrhythmias cause significant morbidity and mortality and pose a major public health problem. They arise from disruptions in the normally orderly propagation of cardiac electrophysiological activation and recovery through successive cardiomyocytes in the heart. They reflect abnormalities in automaticity, initiation, conduction, or recovery in cardiomyocyte excitation.

Nernst-Planck-Gaussian modelling of electrodiffusional recovery from ephaptic excitation between mammalian cardiomyocytes.

In addition to gap junction conduction, recent reports implicate possible ephaptic coupling contributions to action potential (AP) propagation between successive adjacent cardiomyocytes. Here, AP generation in an active cell, withdraws Na from, creating a negative potential within, ephaptic spaces between the participating membranes, the initially quiescent neighbouring cardiomyocyte. However, sustainable ephaptic transmission requires subsequent complete of the ephaptic charge difference.

SARS-CoV-2 Omicron subvariant spike N405 unlikely to rapidly deamidate.

The RGD motif on the SARS-CoV-2 spike protein has been suggested to interact with RGD-binding integrins αVβ3 and α5β1 to enhance viral cell entry and alter downstream signaling cascades. The D405N mutation on the Omicron subvariant spike proteins, resulting in an RGN motif, has recently been shown to inhibit binding to integrin αVβ3. Deamidation of asparagines in protein ligand RGN motifs has been demonstrated to generate RGD and RGisoD motifs that permit binding to RGD-binding integrins.

Feedback contributions to excitation-contraction coupling in native functioning striated muscle.

Skeletal and cardiac muscle excitation-contraction coupling commences with Na1.4/Na1.5-mediated, surface and transverse (T-) tubular, action potential generation.

The β3-subunit modulates the effect of venom peptides ProTx-II and OD1 on Na 1.7 gating.

The voltage-gated sodium channel Na 1.7 is involved in various pain phenotypes and is physiologically regulated by the Na -β3-subunit. Venom toxins ProTx-II and OD1 modulate Na 1.

Cardiac sodium channel complexes and arrhythmia: structural and functional roles of the β1 and β3 subunits.

In cardiac myocytes, the voltage-gated sodium channel Na 1.5 opens in response to membrane depolarisation and initiates the action potential. The Na 1.

In silico analysis of mutations near S1/S2 cleavage site in SARS-CoV-2 spike protein reveals increased propensity of glycosylation in Omicron strain.

Cleavage of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion.

Proteomic analysis in primary T cells reveals IL-7 alters T cell receptor thresholding via CYTIP/cytohesin/LFA-1 localisation and activation.

The ability of the cellular immune system to discriminate self from foreign antigens depends on the appropriate calibration of the T cell receptor (TCR) signalling threshold. The lymphocyte homeostatic cytokine interleukin 7 (IL-7) is known to affect TCR thresholding, but the molecular mechanism is not fully elucidated. A better understanding of this process is highly relevant in the context of autoimmune disease therapy and cancer immunotherapy.

Can the SARS-CoV-2 Spike Protein Bind Integrins Independent of the RGD Sequence?

The RGD motif in the Severe Acute Syndrome Coronavirus 2 (SARS-CoV-2) spike protein has been predicted to bind RGD-recognizing integrins. Recent studies have shown that the spike protein does, indeed, interact with αβ and αβ integrins, both of which bind to RGD-containing ligands. However, computational studies have suggested that binding between the spike RGD motif and integrins is not favourable, even when unfolding occurs after conformational changes induced by binding to the canonical host entry receptor, angiotensin-converting enzyme 2 (ACE2).

Ca2+-dependent modulation of voltage-gated myocyte sodium channels.

Voltage-dependent Na+ channel activation underlies action potential generation fundamental to cellular excitability. In skeletal and cardiac muscle this triggers contraction via ryanodine-receptor (RyR)-mediated sarcoplasmic reticular (SR) Ca2+ release. We here review potential feedback actions of intracellular [Ca2+] ([Ca2+]i) on Na+ channel activity, surveying their structural, genetic and cellular and functional implications, translating these to their possible clinical importance.

Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels.

Voltage-gated sodium (Nav) channels drive the rising phase of the action potential, essential for electrical signalling in nerves and muscles. The Nav channel α-subunit contains the ion-selective pore. In the cardiomyocyte, Nav1.

Identification of the cis‑molecular neighbours of the immune checkpoint protein B7‑H4 in the breast cancer cell‑line SK‑BR‑3 by proteomic proximity labelling.

The immune checkpoint protein B7‑H4 plays an important role in the positive as well as the negative regulation of immune T‑cell responses. When expressed on cancer cells, B7‑H4 inhibits T‑cell activity, and numerous types of cancer cells use upregulation of B7‑H4 as a survival strategy. Thus, B7‑H4 is a potential target for anticancer drug therapy.

Supramolecular clustering of the cardiac sodium channel Nav1.5 in HEK293F cells, with and without the auxiliary β3-subunit.

Voltage-gated sodium channels comprise an ion-selective α-subunit and one or more associated β-subunits. The β3-subunit (encoded by the SCN3B gene) is an important physiological regulator of the heart-specific sodium channel, Nav1.5.

Gating control of the cardiac sodium channel Nav1.5 by its β3-subunit involves distinct roles for a transmembrane glutamic acid and the extracellular domain.

The auxiliary β3-subunit is an important functional regulator of the cardiac sodium channel Nav1.5, and some β3 mutations predispose individuals to cardiac arrhythmias. The β3-subunit uses its transmembrane α-helix and extracellular domain to bind to Nav1.

Multiple targets for flecainide action: implications for cardiac arrhythmogenesis.

Unlabelled: Flecainide suppresses cardiac tachyarrhythmias including paroxysmal atrial fibrillation, supraventricular tachycardia and arrhythmic long QT syndromes (LQTS), as well as the Ca -mediated, catecholaminergic polymorphic ventricular tachycardia (CPVT). However, flecainide can also exert pro-arrhythmic effects most notably following myocardial infarction and when used to diagnose Brugada syndrome (BrS). These divergent actions result from its physiological and pharmacological actions at multiple, interacting levels of cellular organization.

Selective Proteomic Proximity Labeling Assay Using Tyramide (SPPLAT): A Quantitative Method for the Proteomic Analysis of Localized Membrane-Bound Protein Clusters.

This manuscript describes a new and general method to identify proteins localized into spatially restricted membrane microenvironments. Horseradish peroxidase (HRP) is brought into contact with a target protein by being covalently linked to a primary or secondary antibody, an antigen or substrate, a drug, or a toxin. A biotinylated tyramide-based reagent is then added.

Protein Neighbors and Proximity Proteomics.

Within cells, proteins can co-assemble into functionally integrated and spatially restricted multicomponent complexes. Often, the affinities between individual proteins are relatively weak, and proteins within such clusters may interact only indirectly with many of their other protein neighbors. This makes proteomic characterization difficult using methods such as immunoprecipitation or cross-linking.

The chicken B-cell line DT40 proteome, beadome and interactomes.

In developing a new quantitative AP-MS method for exploring interactomes in the chicken B-cell line DT40, we also surveyed the most abundant proteins in this organism and explored the likely contaminants that bind to a variety of affinity resins that would later be confirmed quantitatively [1]. We present the 'Top 150 abundant DT40 proteins list', the DT40 beadomes as well as protein interaction lists for the Phosphatidyl inositol 5-phosphate 4-kinase 2β and Fanconi anaemia protein complexes.

Self-Assembly of Amyloid Fibrils That Display Active Enzymes.

Enzyme immobilization is an important strategy to enhance the stability and recoverability of enzymes and to facilitate the separation of enzymes from reaction products. However, enzyme purification followed by separate chemical steps to allow immobilization on a solid support reduces the efficiency and yield of the active enzyme. Here we describe polypeptide constructs that self-assemble spontaneously into nanofibrils with fused active enzyme subunits displayed on the amyloid fibril surface.

Selective Proteomic Proximity Labeling Assay Using Tyramide (SPPLAT): A Quantitative Method for the Proteomic Analysis of Localized Membrane-Bound Protein Clusters.

This manuscript describes a new and general method to identify proteins localized into spatially restricted membrane microenvironments. Horseradish peroxidase (HRP) is brought into contact with a target protein by being covalently linked to a primary or secondary antibody, an antigen or substrate, a drug, or a toxin. A biotinylated tyramide-based reagent is then added.

A new look at sodium channel β subunits.

Voltage-gated sodium (Nav) channels are intrinsic plasma membrane proteins that initiate the action potential in electrically excitable cells. They are a major focus of research in neurobiology, structural biology, membrane biology and pharmacology. Mutations in Nav channels are implicated in a wide variety of inherited pathologies, including cardiac conduction diseases, myotonic conditions, epilepsy and chronic pain syndromes.