Fungal Shaker-like channels beyond cellular K+ homeostasis: A role in ectomycorrhizal symbiosis between Hebeloma cylindrosporum and Pinus pinaster

Potassium (K+) acquisition, translocation and cellular homeostasis are mediated by various membrane transport systems in all organisms. We identified and described an ion channel in the ectomycorrhizal fungus Hebeloma cylindrosporum (HcSKC) that harbors features of animal voltage-dependent Shaker-like K+ channels, and investigated its role in both free-living hyphae and symbiotic conditions. RNAi lines affected in the expression of HcSKC were produced and used for in vitro mycorrhizal assays with the maritime pine as host plant, under standard or low K+ conditions. The adaptation of H. cylindrosporum to the downregulation of HcSKC was analyzed by qRT-PCR analyses for other K+-related transport proteins: the transporters HcTrk1, HcTrk2, and HcHAK, and the ion channels HcTOK1, HcTOK2.1, and HcTOK2.2. Downregulated HcSKC transformants displayed greater K+ contents at standard K+ only. In such conditions, plants inoculated with these transgenic lines were impaired in K+ nutrition. Taken together, these results support the hypothesis that the reduced expression of HcSKC modifies the pool of fungal K+ available for the plant and/or affects its symbiotic transfer to the roots. Our study reveals that the maintenance of K+ transport in H. cylindrosporum, through the regulation of HcSKC expression, is required for the K+ nutrition of the host plant.

David Christopher Gadsby. 26 March 1947—9 March 2019

Over nearly five decades, David Christopher Gadsby pioneered biophysical research that advanced our mechanistic understanding of ion-transporting proteins in biological membranes. His passion for hands-on do-it-yourself electrophysiology, his depth of analytical rigor, and his idiosyncratic scientific aesthetic expanded the edge of discovery in two areas: the electrical character of the Na + pump, and the molecular workings of ‘cystic fibrosis transmembrane regulator’ (CFTR), the chloride ion channel whose mutations cause cystic fibrosis. His approach was flavoured by an appreciation for common underlying features between these ostensibly distinct types of membrane-transport systems. While David's focus was first on the basic molecular biophysics of a problem, he was always attuned to implications of his discoveries for human health. Based in New York at The Rockefeller University throughout his independent scientific career, and at the Marine Biological Laboratory in Woods Hole, Massachusetts, as a squid-season research-scientist, he was proficient in wrestling with problems spanning a wide swath of membrane biology: from determinants of the cardiac electrical waveform, to microsecond-timescale ionic currents in squid axons, to details of structure–mechanism relations in membrane pump and ion-channel proteins. He wore his eminence lightly and never distanced himself from the laboratory, where he often performed experiments with his own hands right up to his retirement. His reserved scientific personality, which demanded equally from his colleagues and himself immaculate data, unclouded logic, and substantive pertinence to the issues at hand, contrasted with his palpable joy in a good experiment and in his sea-loving life outside the lab.

Is there any association between manganese level and schizophrenia? - a descriptive review

Introduction: Manganese has a role in the membrane transport systems, synthesis of protein, vitamin C, and vitamins B, catalysis of hematopoiesis, regulation of the endocrine, immune system, blood sugar, reproduction, digestion, and blood coagulation. Furthermore, the level of manganese concentrations in human body appears to affect the occurrence of schizophrenia. The aim of this study was to search for relationships between the manganese level and the onset of schizophrenia.Material and methods: A descriptive review was performed based on a literature search on Medline and Google scholar from 2003 to 2020, using keywords: schizophrenia, manganese, Mn. The included studies were meta-analyses, case-control studies, and cohort studies that examined differences in manganese concentrations in patients with schizophrenia and healthy controls.Result: Eight studies were selected for the review, with one reporting elevated levels of manganese, two showing no significant differences, and the rest including two meta-analyses stating lower manganese concentrations in patients with schizophrenia in comparison with controls.Conclusion: In most of the researched studies, manganese concentrations in patients with schizophrenia were lower than in control groups, but not all of them reached the same conclusions. The relationship between manganese levels and schizophrenia must be further investigated.

Voltage-Switchable HCl Transporters: The Effect of Lipid Headgroup Binding

Synthetic anion transporters that facilitate transmembrane H⁺/Cl^-symport (cotransport)have anti-cancer potential due to their ability to neutralize pH gradients and inhibit autophagy in cells. However, compared to the natural product prodigiosin, synthetic anion transporters have low-to-modest H⁺/Cl^-symportactivity and their mechanism of action remains less well understood. We here report a chloride-selective tetraurea macrocycle that has a record-high H⁺/Cl^-symportactivity similar to prodigiosin and most importantly demonstrates unprecedented voltage-switchable transport properties that is linked to the lack of uniport activity. By studying anion binding affinity and transport mechanisms of four other anion transporters, we show that the lack of uniport and the voltage-dependent H⁺/Cl^-symport originate from strong binding to lipid phosphate headgroup that hampers the diffusion of the free transporters through the membranes, leading to an unusual H⁺/Cl^-symport mechanism that involves only charged species. Our work provides important mechanistic insights into different classes of anion transporters and a new approach to achieve voltage-switchability in artificial membrane transport systems.

Voltage-Switchable HCl Transporters: The Effect of Lipid Headgroup Binding

Synthetic anion transporters that facilitate transmembrane H⁺/Cl^-symport (cotransport)have anti-cancer potential due to their ability to neutralize pH gradients and inhibit autophagy in cells. However, compared to the natural product prodigiosin, synthetic anion transporters have low-to-modest H⁺/Cl^-symportactivity and their mechanism of action remains less well understood. We here report a chloride-selective tetraurea macrocycle that has a record-high H⁺/Cl^-symportactivity similar to prodigiosin and most importantly demonstrates unprecedented voltage-switchable transport properties that is linked to the lack of uniport activity. By studying anion binding affinity and transport mechanisms of four other anion transporters, we show that the lack of uniport and the voltage-dependent H⁺/Cl^-symport originate from strong binding to lipid phosphate headgroup that hampers the diffusion of the free transporters through the membranes, leading to an unusual H⁺/Cl^-symport mechanism that involves only charged species. Our work provides important mechanistic insights into different classes of anion transporters and a new approach to achieve voltage-switchability in artificial membrane transport systems.

Guard Cell Membrane Anion Transport Systems and Their Regulatory Components: An Elaborate Mechanism Controlling Stress-Induced Stomatal Closure

When plants are exposed to drastic environmental changes such as drought, salt or bacterial invasion, rapid stomatal movement confers tolerance to these stresses. This process involves a variety of guard cell expressed ion channels and their complex regulation network. Inward K+ channels mainly function in stomatal opening. On the other hand, guard cell anion channels play a crucial role in the closing of stomata, which is vital in terms of preventing water loss and bacterial entrance. Massive progress has been made on the research of these anion channels in the last decade. In this review, we focus on the function and regulation of Arabidopsis guard cell anion channels. Starting from SLAC1, a main contributor of stomatal closure, members of SLAHs (SLAC1 homologues), AtNRTs (Nitrate transporters), AtALMTs (Aluminum-activated malate transporters), ABC transporters, AtCLCs (Chloride channels), DTXs (Detoxification efflux carriers), SULTRs (Sulfate transporters), and their regulator components are reviewed. These membrane transport systems are the keys to maintaining cellular ion homeostasis against fluctuating external circumstances.

Erythrocyte Senescence in a Model of Rat Displaying Hutchinson-Gilford Progeria Syndrome

Background.Increased oxidative stress is a major cause of aging and age-related diseases. Erythrocytes serve as good model for aging studies. Dihydrotachysterol is known to induce premature aging feature in rats mimicking Hutchinson-Gilford progeria syndrome.Aim.In the present study, attempts have been made to explore the differential response of young and senescent erythrocytes separated by density gradient centrifugation from accelerated senescence model of rats mimicking Hutchinson-Gilford progeria syndrome and naturally aged rats.Methods.The erythrocytes of naturally aged and progeroid rats were separated into distinct, young and old cells on the basis of their differential densities. The parameters of oxidative stress and membrane transport systems were studied.Discussion and Conclusion.Our study provides evidence that organismal aging negatively affects oxidative stress markers and membrane transport systems in both young and old erythrocytes. This study further substantiates that the changes in progeria model of rats resemble natural aging in terms of erythrocyte senescence.

The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to a chronic inflammatory reaction. It is one of the most widespread gynecological diseases with a 10–15% prevalence in the general female population, rising up to 30–45% in patients with infertility. Although it was first described in 1860, its etiology and pathogenesis are still unclear. It is now accepted that inflammation plays a central role in the development and progression of endometriosis. In particular, it is marked by an inflammatory process associated with the overproduction of an array of inflammatory mediators such as prostaglandins, metalloproteinases, cytokines, and chemokines. In addition, the growth and adhesion of endometrial cells in the peritoneal cavity due to reactive oxygen species (ROS) and free radicals lead to disease onset, its ensuing symptoms—among which pain and infertility. The aim of our review is to evaluate the role of oxidative stress and ROS in the pathogenesis of endometriosis and the efficacy of antioxidant therapy in the treatment and mitigation of its symptoms.