Membrane Channels and Transporters

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Functions".

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 25972

Special Issue Editors


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Guest Editor
Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz, Austria
Interests: protein engineering; protein oligomerization; protein-protein interactions; protein-lipid interactions; small molecule transport; aquaporins; urea channels

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Guest Editor
Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz, Austria
Interests: protein translocation; translocon; single channel electrophysiology; surface proton; protein-lipid interactions
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Guest Editor
Department of Biosystems Science and Engineering, Eidgenössiche Technische Hochschule (ETH) Zürich, Mattenstr. 26, 4058 Basel, Switzerland
Interests: molecular dynamics simulations; multiscaling; method development; biological processes; biomembranes; proteins; post-translational modifications; GPCRs; membrane insertion; protein dimerization; transport
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Membrane channels facilitate passive solute and solvent transport across biomembranes and are of utmost physiological importance. Their selectivity, transport rate, and substrate size vary widely ranging from highly efficient and selective aquaporins or ion channels, which can accommodate only water molecules or ions in single-file fashion respectively, to large non-specific transmembrane pores such as porins and gasdermins. Transporters such as uniporters, symporters and antiporters, are responsible for active transport.

The rapid development of experimental and in silico methods such as cryoEM, MS, high speed AFM, super-resolution microscopy, electrophysiology and molecular dynamics simulations, to name a few, have recently brought new insight on diverse regulation mechanisms of membrane channel and transporter function. Growing attention is brought to the influence of the lipid bilayer on protein structure and function, including specific protein-lipid interactions and the mechanical parameters of the lipid matrix housing the respective membrane proteins. Thereby, new physical models appear which account for the membrane effect on the complex channel behaviour and suggest how conformational changes can be transferred between domains over large scales.

In this Special Issue, we want to focus on the recent achievements in the field and invite you to submit reviews and original research papers further advancing our knowledge on the structure, function, and regulation of membrane channels and transporters by in-vivo, in-vitro, or in-silico investigations. In this context, we will also consider methodological developments and advancements used to study membrane channels and transporters.

Dr. Andreas Horner
Dr. Denis G. Knyazev
Dr. Kristyna Pluhackova
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Membrane permeability
  • Aqua(glycero)porins
  • Ion channels
  • Transporters
  • Membrane channel regulation and gating
  • Protein-lipid interactions
  • Protein oligomerization
  • Protein translocation
  • Transmembrane transport of large cargo molecules
  • Holins
  • Pore-forming toxis
  • Gasdermins
  • Artificial lipid bilayers
  • Protein reconstitution

Published Papers (6 papers)

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Research

Jump to: Review

16 pages, 1747 KiB  
Article
Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle
by Klaus Schicker, Shreyas Bhat, Clemens Farr, Verena Burtscher, Andreas Horner, Michael Freissmuth and Walter Sandtner
Membranes 2021, 11(3), 178; https://doi.org/10.3390/membranes11030178 - 3 Mar 2021
Cited by 6 | Viewed by 2046
Abstract
Plasmalemmal solute carriers (SLCs) gauge and control solute abundance across cellular membranes. By virtue of this action, they play an important role in numerous physiological processes. Mutations in genes encoding the SLCs alter amino acid sequence that often leads to impaired [...] Read more.
Plasmalemmal solute carriers (SLCs) gauge and control solute abundance across cellular membranes. By virtue of this action, they play an important role in numerous physiological processes. Mutations in genes encoding the SLCs alter amino acid sequence that often leads to impaired protein function and onset of monogenic disorders. To understand how these altered proteins cause disease, it is necessary to undertake relevant functional assays. These experiments reveal descriptors of SLC function such as the maximal transport velocity (Vmax), the Michaelis constant for solute uptake (KM), potencies for inhibition of transporter function (IC50/EC50), and many more. In several instances, the mutated versions of different SLC transporters differ from their wild-type counterparts in the value of these descriptors. While determination of these experimental parameters can provide conjecture as to how the mutation gives rise to disease, they seldom provide any definitive insights on how a variant differ from the wild-type transporter in its operation. This is because the experimental determination of association between values of the descriptors and several partial reactions a transporter undergoes is casual, but not causal, at best. In the present study, we employ kinetic models that allow us to derive explicit mathematical terms and provide experimental descriptors as a function of the rate constants used to parameterize the kinetic model of the transport cycle. We show that it is possible to utilize these mathematical expressions to deduce, from experimental outcomes, how the mutation has impinged on partial reactions in the transport cycle. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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20 pages, 5619 KiB  
Article
Membrane-Mediated Lateral Interactions Regulate the Lifetime of Gramicidin Channels
by Oleg V. Kondrashov, Timur R. Galimzyanov, Rodion J. Molotkovsky, Oleg V. Batishchev and Sergey A. Akimov
Membranes 2020, 10(12), 368; https://doi.org/10.3390/membranes10120368 - 25 Nov 2020
Cited by 7 | Viewed by 1859
Abstract
The lipid matrix of cellular membranes is an elastic liquid crystalline medium. Its deformations regulate the functionality and interactions of membrane proteins,f membrane-bound peptides, lipid and protein-lipid domains. Gramicidin A (gA) is a peptide, which incorporates into membrane leaflets as a monomer and [...] Read more.
The lipid matrix of cellular membranes is an elastic liquid crystalline medium. Its deformations regulate the functionality and interactions of membrane proteins,f membrane-bound peptides, lipid and protein-lipid domains. Gramicidin A (gA) is a peptide, which incorporates into membrane leaflets as a monomer and may form a transmembrane dimer. In both configurations, gA deforms the membrane. The transmembrane dimer of gA is a cation-selective ion channel. Its electrical response strongly depends on the elastic properties of the membrane. The gA monomer and dimer deform the membrane differently; therefore, the elastic energy contributes to the activation barriers of the dimerization and dissociation of the conducting state. It is shown experimentally that channel characteristics alter if gA molecules have been located in the vicinity of the conducting dimer. Here, based on the theory of elasticity of lipid membranes, we developed a quantitative theoretical model which allows explaining experimentally observed phenomena under conditions of high surface density of gA or its analogues, i.e., in the regime of strong lateral interactions of gA molecules, mediated by elastic deformations of the membrane. The model would be useful for the analysis and prediction of the gA electrical response in various experimental conditions. This potentially widens the possible applications of gA as a convenient molecular sensor of membrane elasticity. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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12 pages, 2973 KiB  
Article
Transmembrane Facilitation of Lactate/H+ Instead of Lactic Acid Is Not a Question of Semantics but of Cell Viability
by Annika Bader and Eric Beitz
Membranes 2020, 10(9), 236; https://doi.org/10.3390/membranes10090236 - 15 Sep 2020
Cited by 15 | Viewed by 3435
Abstract
Transmembrane transport of monocarboxylates is conferred by structurally diverse membrane proteins. Here, we describe the pH dependence of lactic acid/lactate facilitation of an aquaporin (AQP9), a monocarboxylate transporter (MCT1, SLC16A1), and a formate–nitrite transporter (plasmodium falciparum FNT, PfFNT) in the equilibrium transport state. [...] Read more.
Transmembrane transport of monocarboxylates is conferred by structurally diverse membrane proteins. Here, we describe the pH dependence of lactic acid/lactate facilitation of an aquaporin (AQP9), a monocarboxylate transporter (MCT1, SLC16A1), and a formate–nitrite transporter (plasmodium falciparum FNT, PfFNT) in the equilibrium transport state. FNTs exhibit a channel-like structure mimicking the aquaporin-fold, yet act as secondary active transporters. We used radiolabeled lactate to monitor uptake via yeast-expressed AQP9, MCT1, and PfFNT for long enough time periods to reach the equilibrium state in which import and export rates are balanced. We confirmed that AQP9 behaved perfectly equilibrative for lactic acid, i.e., the neutral lactic acid molecule enters and passes the channel. MCT1, in turn, actively used the transmembrane proton gradient and acted as a lactate/H+ co-transporter. PfFNT behaved highly similar to the MCT in terms of transport properties, although it does not adhere to the classical alternating access transporter model. Instead, the FNT appears to use the proton gradient to neutralize the lactate anion in the protein’s vestibule to generate lactic acid in a place that traverses the central hydrophobic transport path. In conclusion, we propose to include FNT-type proteins into a more generalized, function-based transporter definition. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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Review

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61 pages, 5896 KiB  
Review
Molecular Choreography and Structure of Ca2+ Release-Activated Ca2+ (CRAC) and KCa2+ Channels and Their Relevance in Disease with Special Focus on Cancer
by Adéla Tiffner and Isabella Derler
Membranes 2020, 10(12), 425; https://doi.org/10.3390/membranes10120425 - 15 Dec 2020
Cited by 9 | Viewed by 4274
Abstract
Ca2+ ions play a variety of roles in the human body as well as within a single cell. Cellular Ca2+ signal transduction processes are governed by Ca2+ sensing and Ca2+ transporting proteins. In this review, we discuss the Ca [...] Read more.
Ca2+ ions play a variety of roles in the human body as well as within a single cell. Cellular Ca2+ signal transduction processes are governed by Ca2+ sensing and Ca2+ transporting proteins. In this review, we discuss the Ca2+ and the Ca2+-sensing ion channels with particular focus on the structure-function relationship of the Ca2+ release-activated Ca2+ (CRAC) ion channel, the Ca2+-activated K+ (KCa2+) ion channels, and their modulation via other cellular components. Moreover, we highlight their roles in healthy signaling processes as well as in disease with a special focus on cancer. As KCa2+ channels are activated via elevations of intracellular Ca2+ levels, we summarize the current knowledge on the action mechanisms of the interplay of CRAC and KCa2+ ion channels and their role in cancer cell development. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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32 pages, 1194 KiB  
Review
Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins
by Natalia Naumova and Radek Šachl
Membranes 2020, 10(10), 299; https://doi.org/10.3390/membranes10100299 - 21 Oct 2020
Cited by 25 | Viewed by 4959
Abstract
Mitochondria represent the fundamental system for cellular energy metabolism, by not only supplying energy in the form of ATP, but also by affecting physiology and cell death via the regulation of calcium homeostasis and the activity of Bcl-2 proteins. A lot of research [...] Read more.
Mitochondria represent the fundamental system for cellular energy metabolism, by not only supplying energy in the form of ATP, but also by affecting physiology and cell death via the regulation of calcium homeostasis and the activity of Bcl-2 proteins. A lot of research has recently been devoted to understanding the interplay between Bcl-2 proteins, the regulation of these interactions within the cell, and how these interactions lead to the changes in calcium homeostasis. However, the role of Bcl-2 proteins in the mediation of mitochondrial calcium homeostasis, and therefore the induction of cell death pathways, remain underestimated and are still not well understood. In this review, we first summarize our knowledge about calcium transport systems in mitochondria, which, when miss-regulated, can induce necrosis. We continue by reviewing and analyzing the functions of Bcl-2 proteins in apoptosis. Finally, we link these two regulatory mechanisms together, exploring the interactions between the mitochondrial Ca2+ transport systems and Bcl-2 proteins, both capable of inducing cell death, with the potential to determine the cell death pathway—either the apoptotic or the necrotic one. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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46 pages, 4504 KiB  
Review
Cu Homeostasis in Bacteria: The Ins and Outs
by Andreea Andrei, Yavuz Öztürk, Bahia Khalfaoui-Hassani, Juna Rauch, Dorian Marckmann, Petru-Iulian Trasnea, Fevzi Daldal and Hans-Georg Koch
Membranes 2020, 10(9), 242; https://doi.org/10.3390/membranes10090242 - 18 Sep 2020
Cited by 59 | Viewed by 8050
Abstract
Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which [...] Read more.
Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells. Full article
(This article belongs to the Special Issue Membrane Channels and Transporters)
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