Potential Theranostic Roles of SLC4 Molecules in Human Diseases.

The solute carrier family 4 (SLC4) is an important protein responsible for the transport of various ions across the cell membrane and mediating diverse physiological functions, such as the ion transporting function, protein-to-protein interactions, and molecular transduction. The deficiencies in SLC4 molecules may cause multisystem disease involving, particularly, the respiratory system, digestive, urinary, endocrine, hematopoietic, and central nervous systems. Currently, there are no effective strategies to treat these diseases. SLC4 proteins are also found to contribute to tumorigenesis and development, and some of them are regarded as therapeutic targets in quite a few clinical trials. This indicates that SLC4 proteins have potential clinical prospects. In view of their functional characteristics, there is a critical need to review the specific functions of bicarbonate transporters, their related diseases, and the involved pathological mechanisms. We summarize the diseases caused by the mutations in SLC4 family genes and briefly introduce the clinical manifestations of these diseases as well as the current treatment strategies. Additionally, we illustrate their roles in terms of the physiology and pathogenesis that has been currently researched, which might be the future therapeutic and diagnostic targets of diseases and a new direction for drug research and development.

Epithelial Transport in Disease: An Overview of Pathophysiology and Treatment.

Epithelial transport is a multifaceted process crucial for maintaining normal physiological functions in the human body. This comprehensive review delves into the pathophysiological mechanisms underlying epithelial transport and its significance in disease pathogenesis. Beginning with an introduction to epithelial transport, it covers various forms, including ion, water, and nutrient transfer, followed by an exploration of the processes governing ion transport and hormonal regulation. The review then addresses genetic disorders, like cystic fibrosis and Bartter syndrome, that affect epithelial transport. Furthermore, it investigates the involvement of epithelial transport in the pathophysiology of conditions such as diarrhea, hypertension, and edema. Finally, the review analyzes the impact of renal disease on epithelial transport and highlights the potential for future research to uncover novel therapeutic interventions for conditions like cystic fibrosis, hypertension, and renal failure.

A blue-shifted anion channelrhodopsin from the Colpodellida alga Vitrella brassicaformis.

Microbial rhodopsins, a family of photoreceptive membrane proteins containing the chromophore retinal, show a variety of light-dependent molecular functions. Channelrhodopsins work as light-gated ion channels and are widely utilized for optogenetics, which is a method for controlling neural activities by light. Since two cation channelrhodopsins were identified from the chlorophyte alga Chlamydomonas reinhardtii, recent advances in genomic research have revealed a wide variety of channelrhodopsins including anion channelrhodopsins (ACRs), describing their highly diversified molecular properties (e.g., spectral sensitivity, kinetics and ion selectivity). Here, we report two channelrhodopsin-like rhodopsins from the Colpodellida alga Vitrella brassicaformis, which are phylogenetically distinct from the known channelrhodopsins. Spectroscopic and electrophysiological analyses indicated that these rhodopsins are green- and blue-sensitive pigments (λmax = ~ 550 and ~ 440 nm) that exhibit light-dependent ion channeling activities. Detailed electrophysiological analysis revealed that one of them works as a monovalent anion (Cl-, Br- and NO3-) channel and we named it V. brassicaformis anion channelrhodopsin-2, VbACR2. Importantly, the absorption maximum of VbACR2 (~ 440 nm) is blue-shifted among the known ACRs. Thus, we identified the new blue-shifted ACR, which leads to the expansion of the molecular diversity of ACRs.

Molecular Physiological Evidence for the Role of Na+-Cl- Co-Transporter in Branchial Na+ Uptake in Freshwater Teleosts.

The gills are the major organ for Na+ uptake in teleosts. It was proposed that freshwater (FW) teleosts adopt Na+/H+ exchanger 3 (Nhe3) as the primary transporter for Na+ uptake and Na+-Cl- co-transporter (Ncc) as the backup transporter. However, convincing molecular physiological evidence to support the role of Ncc in branchial Na+ uptake is still lacking due to the limitations of functional assays in the gills. Thus, this study aimed to reveal the role of branchial Ncc in Na+ uptake with an in vivo detection platform (scanning ion-selective electrode technique, SIET) that has been recently established in fish gills. First, we identified that Ncc2-expressing cells in zebrafish gills are a specific subtype of ionocyte (NCC ionocytes) by using single-cell transcriptome analysis and immunofluorescence. After a long-term low-Na+ FW exposure, zebrafish increased branchial Ncc2 expression and the number of NCC ionocytes and enhanced gill Na+ uptake capacity. Pharmacological treatments further suggested that Na+ is indeed taken up by Ncc, in addition to Nhe, in the gills. These findings reveal the uptake roles of both branchial Ncc and Nhe under FW and shed light on osmoregulatory physiology in adult fish.

Ablation of TRPC3 compromises bicarbonate and phosphate transporter activity in mice proximal tubular cells.

Proximal tubular (PT) cells reabsorb most calcium (Ca2+ ), phosphate (PO4 3- ), bicarbonate (HCO3 - ), and oxalate (C2 O4 2- ) ions. We have shown that mice lacking Transient Receptor Potential Canonical 3 (TRPC3-/- ) channel are moderately hypercalciuric with presentation of luminal calcium phosphate (CaP) crystals at the loop of Henle (LOH). However, other predisposing factors for such crystal deposition are unknown. Thus, we examined the distinctions in functional status of HCO3 - , PO4 3- , and C2 O4 2- transporters in PT cells of wild type (WT) and TRPC3-/- mice by whole-cell patch clamp techniques to assess their contribution in the development of LOH CaP crystals. Here we show the development of concentration dependent HCO3 - -induced currents in all PT cells, which was confirmed by using specific HCO3 - channel inhibitor, S0859. Interestingly, such activities were diminished in PT cells from TRPC3-/- mice, suggesting reduced HCO3 - transport in absence of TRPC3. While PO4 3- -induced currents were also concentration dependent in all PT cells (confirmed by PO4 3- channel inhibitor, PF-06869206), those activities were reduced in absence of TRPC3, suggesting lower PO4 3- reabsorption that can leave excess luminal PO4 3- . Next, we applied thiosulfate (O3 S2 2 - ) as a competitive inhibitor of the SLC26a6 transporter upon C2 O4 2- current activation and observed a reduced C2 O4 2- -induced conductance which was greater in TRPC3-/- PT cells. Together, these results suggest that the reduced activities of HCO3 - , PO4 3- , and C2 O4 2- transporters in moderately hypercalciuric (TRPC3-/- ) PT cells can create a predisposing condition for CaP and CaP tubular crystallization, enabling CaP crystal formation in LOH of TRPC3-/- mice.

Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-Cl- cotransporters.

Bone turnover diseases are exceptionally prevalent in human and come with a high burden on physical health. While these diseases are associated with a variety of risk factors and causes, they are all characterized by common denominators, that is, abnormalities in the function or number of osteoblasts, osteoclasts, and/or osteocytes. As such, much effort has been deployed in the recent years to understand the signaling mechanisms of bone cell proliferation and differentiation with the objectives of exploiting the intermediates involved as therapeutic preys. Ion transport systems at the external and in the intracellular membranes of osteoblasts and osteoclasts also play an important role in bone turnover by coordinating the movement of Ca2+ , PO4 2- , and H+ ions in and out of the osseous matrix. Even if they sustain the terminal steps of osteoformation and osteoresorption, they have been the object of very little attention in the last several years. Members of the cation-Cl- cotransporter (CCC) family are among the systems at work as they are expressed in bone cells, are known to affect the activity of Ca2+ -, PO4 2- -, and H+ -dependent transport systems and have been linked to bone mass density variation in human. In this review, the roles played by the CCCs in bone remodeling will be discussed in light of recent developments and their potential relevance in the treatment of skeletal disorders.

Prokaryotic Na+/H+ Exchangers-Transport Mechanism and Essential Residues.

Na+/H+ exchangers are essential for Na+ and pH homeostasis in all organisms. Human Na+/H+ exchangers are of high medical interest, and insights into their structure and function are aided by the investigation of prokaryotic homologues. Most prokaryotic Na+/H+ exchangers belong to either the Cation/Proton Antiporter (CPA) superfamily, the Ion Transport (IT) superfamily, or the Na+-translocating Mrp transporter superfamily. Several structures have been solved so far for CPA and Mrp members, but none for the IT members. NhaA from E. coli has served as the prototype of Na+/H+ exchangers due to the high amount of structural and functional data available. Recent structures from other CPA exchangers, together with diverse functional information, have allowed elucidation of some common working principles shared by Na+/H+ exchangers from different families, such as the type of residues involved in the substrate binding and even a simple mechanism sufficient to explain the pH regulation in the CPA and IT superfamilies. Here, we review several aspects of prokaryotic Na+/H+ exchanger structure and function, discussing the similarities and differences between different transporters, with a focus on the CPA and IT exchangers. We also discuss the proposed transport mechanisms for Na+/H+ exchangers that explain their highly pH-regulated activity profile.

Role of inwardly rectifying K+ channel 5.1 (Kir5.1) in the regulation of renal membrane transport.

PURPOSE OF REVIEW: Kir5.1 interacts with Kir4.2 in proximal tubule and with Kir4.1 in distal convoluted tubule (DCT), connecting tubule (CNT) and cortical collecting duct (CCD) to form basolateral-K+-channels. Kir4.2/Kir5.1 and Kir4.1/Kir5.1 play an important role in regulating Na+/HCO3--transport of the proximal tubule and Na+/K+ -transport in the DCT/CNT/CCD. The main focus of this review is to provide an overview of the recent development in the field regarding the role of Kir5.1 regulating renal electrolyte transport in the proximal tubule and DCT. RECENT FINDINGS: Loss-of-function-mutations of KCNJ16 cause a new form of tubulopathy, characterized by hypokalaemia, Na+-wasting, acid-base-imbalance and metabolic-acidosis. Abnormal bicarbonate transport induced by loss-of-function of KCNJ16-mutants is recapitulated in Kir4.2-knockout-(Kir4.2 KO) mice. Deletion of Kir5.1 also abolishes the effect of dietary Na+ and K+-intakes on the basolateral membrane voltage and NCC expression/activity. Long-term high-salt intake or high-K+-intake causes hyperkalaemic in Kir5.1-deficient mice. SUMMARY: Kir4.2/Kir5.1 activity in the proximal tubule plays a key role in regulating Na+, K+ and bicarbonate-transport through regulating electrogenic-Na+-bicarbonate-cotransporter-(NBCe1) and type 3-Na+/H+-exchanger-(NHE3). Kir4.1/Kir5.1 activity of the DCT plays a critical role in mediating the effect of dietary-K+ and Na+-intakes on NCC activity/expression. As NCC determines the Na+ delivery rate to the aldosterone-sensitive distal nephron (ASDN), defective regulation of NCC during high-salt and high-K+ compromises renal K+ excretion and K+ homeostasis.

Transmembrane serine protease 2 (TMPRSS2) proteolytically activates the epithelial sodium channel (ENaC) by cleaving the channel's γ-subunit.

The epithelial sodium channel (ENaC) is a heterotrimer consisting of α-, ß-, and γ-subunits. Channel activation requires proteolytic release of inhibitory tracts from the extracellular domains of α-ENaC and γ-ENaC; however, the proteases involved in the removal of the γ-inhibitory tract remain unclear. In several epithelial tissues, ENaC is coexpressed with the transmembrane serine protease 2 (TMPRSS2). Here, we explored the effect of human TMPRSS2 on human αßγ-ENaC heterologously expressed in Xenopus laevis oocytes. We found that coexpression of TMPRSS2 stimulated ENaC-mediated whole-cell currents by approximately threefold, likely because of an increase in average channel open probability. Furthermore, TMPRSS2-dependent ENaC stimulation was not observed using a catalytically inactive TMPRSS2 mutant and was associated with fully cleaved γ-ENaC in the intracellular and cell surface protein fractions. This stimulatory effect of TMPRSS2 on ENaC was partially preserved when inhibiting its proteolytic activity at the cell surface using aprotinin but was abolished when the γ-inhibitory tract remained attached to its binding site following introduction of two cysteine residues (S155C-Q426C) to form a disulfide bridge. In addition, computer simulations and site-directed mutagenesis experiments indicated that TMPRSS2 can cleave γ-ENaC at sites both proximal and distal to the γ-inhibitory tract. This suggests a dual role of TMPRSS2 in the proteolytic release of the γ-inhibitory tract. Finally, we demonstrated that TMPRSS2 knockdown in cultured human airway epithelial cells (H441) reduced baseline proteolytic activation of endogenously expressed ENaC. Thus, we conclude that TMPRSS2 is likely to contribute to proteolytic ENaC activation in epithelial tissues in vivo.

Blending physiology and RNAseq to provide new insights into regulation of epithelial transport: switching between ion secretion and reabsorption.

This Review addresses the means by which epithelia change the direction of vectorial ion transport. Recent studies have revealed that insect Malpighian (renal) tubules can switch from secreting to reabsorbing K+. When the gut of larval lepidopterans is empty (during the moult cycle) or when the larvae are reared on K+-deficient diet, the distal ileac plexus segment of the tubule secretes K+ from the haemolymph into the tubule lumen. By contrast, in larvae reared on K+-rich diet, ions and fluid are reabsorbed from the rectal lumen into the perinephric space surrounding the cryptonephridial tubules of the rectal complex. Ions and fluid are then transported from the perinephric space into the lumen of the cryptonephridial tubules, thus supplying the free segments of the tubule downstream. Under these conditions, some of the K+ and water in the tubule lumen is reabsorbed across the cells of the distal ileac plexus, allowing for expansion of haemolymph volume in the rapidly growing larvae, as well as recycling of K+ and base equivalents. RNA sequencing data reveal large-scale changes in gene transcription that are associated with the switch between ion secretion and ion reabsorption by the distal ileac plexus. An unexpected finding is the presence of voltage-gated, ligand-gated and mechanosensitive ion channels, normally seen in excitable cells, in Malpighian tubules. Transcriptomic surveys indicate that these types of channels are also present in multiple other types of vertebrate and invertebrate epithelia, suggesting that they may play novel roles in epithelial cell signalling and regulation of epithelial ion transport.

Polymodal Control of TMEM16x Channels and Scramblases.

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 Ca2+ release evoked by Gq-protein-coupled receptor (GqPCR) activation; thus, TMEM16x proteins link Ca2+-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.

Structural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1.

Flycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is a larger protein and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterize FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion preference and conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt 'up' or 'down' conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.

A review on bacterial redox dependent iron transporters and their evolutionary relationship.

Iron is an essential yet toxic micronutrient and its transport across biological membranes is tightly regulated in all living organisms. One such iron transporter, the Ftr-type permeases, is found in both eukaryotic and prokaryotic cells. These Ftr-type transporters are required for iron transport, predicted to form α-helical transmembrane structures, and conserve two ArgGluxxGlu (x = any amino acid) motifs. In the yeast Ftr transporter (Ftr1p), a ferroxidase (Fet3p) is required for iron transport in an oxidation coupled transport step. None of the bacterial Ftr-type transporters (EfeU and FetM from E. coli; cFtr from Campylobacter jejuni; FtrC from Brucella, Bordetella, and Burkholderia spp.) contain a ferroxidase protein. Bioinformatics report predicted periplasmic EfeO and FtrB (from the EfeUOB and FtrABCD systems) as novel cupredoxins. The Cu2+ binding and the ferrous oxidation properties of these proteins are uncharacterized and the other two bacterial Ftr-systems are expressed without any ferroxidase/cupredoxin, leading to controversy about the mode of function of these transporters. Here, we review published data on Ftr-type transporters to gain insight into their functional diversity. Based on original bioinformatics data presented here evolutionary relations between these systems are presented.

Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.

The plasma-membrane homeostasis Na+/Ca2+ exchangers (NCXs) mediate Ca2+ extrusion/entry to dynamically shape Ca2+ signaling/in biological systems ranging from bacteria to humans. The NCX gene orthologs, isoforms, and their splice variants are expressed in a tissue-specific manner and exhibit nearly 104-fold differences in the transport rates and regulatory specificities to match the cell-specific requirements. Selective pharmacological targeting of NCX variants could benefit many clinical applications, although this intervention remains challenging, mainly because a full-size structure of eukaryotic NCX is unavailable. The crystal structure of the archaeal NCX_Mj, in conjunction with biophysical, computational, and functional analyses, provided a breakthrough in resolving the ion transport mechanisms. However, NCX_Mj (whose size is nearly three times smaller than that of mammalian NCXs) cannot serve as a structure-dynamic model for imitating high transport rates and regulatory modules possessed by eukaryotic NCXs. The crystal structures of isolated regulatory domains (obtained from eukaryotic NCXs) and their biophysical analyses by SAXS, NMR, FRET, and HDX-MS approaches revealed structure-based variances of regulatory modules. Despite these achievements, it remains unclear how multi-domain interactions can decode and integrate diverse allosteric signals, thereby yielding distinct regulatory outcomes in a given ortholog/isoform/splice variant. This article summarizes the relevant issues from the perspective of future developments.

Proteolytic activation of the epithelial sodium channel (ENaC) by factor VII activating protease (FSAP) and its relevance for sodium retention in nephrotic mice.

Proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases is thought to contribute to renal sodium retention in nephrotic syndrome. However, the identity of the responsible proteases remains elusive. This study evaluated factor VII activating protease (FSAP) as a candidate in this context. We analyzed FSAP in the urine of patients with nephrotic syndrome and nephrotic mice and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in FSAP-deficient mice (Habp2-/-) with experimental nephrotic syndrome induced by doxorubicin. In urine samples from nephrotic humans, high concentrations of FSAP were detected both as zymogen and in its active state. Recombinant serine protease domain of FSAP stimulated ENaC-mediated whole-cell currents in a time- and concentration-dependent manner. Mutating the putative prostasin cleavage site in γ-ENaC (γRKRK178AAAA) prevented channel stimulation by the serine protease domain of FSAP. In a mouse model for nephrotic syndrome, active FSAP was present in nephrotic urine of Habp2+/+ but not of Habp2-/- mice. However, Habp2-/- mice were not protected from sodium retention compared to nephrotic Habp2+/+ mice. Western blot analysis revealed that in nephrotic Habp2-/- mice, proteolytic cleavage of α- and γ-ENaC was similar to that in nephrotic Habp2+/+ animals. In conclusion, active FSAP is excreted in the urine of nephrotic patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site of γ-ENaC. However, endogenous FSAP is not essential for sodium retention in nephrotic mice.

Regulation of Cytosolic pH: The Contributions of Plant Plasma Membrane H+-ATPases and Multiple Transporters.

Cytosolic pH homeostasis is a precondition for the normal growth and stress responses in plants, and H+ flux across the plasma membrane is essential for cytoplasmic pH control. Hence, this review focuses on seven types of proteins that possess direct H+ transport activity, namely, H+-ATPase, NHX, CHX, AMT, NRT, PHT, and KT/HAK/KUP, to summarize their plasma-membrane-located family members, the effect of corresponding gene knockout and/or overexpression on cytosolic pH, the H+ transport pathway, and their functional regulation by the extracellular/cytosolic pH. In general, H+-ATPases mediate H+ extrusion, whereas most members of other six proteins mediate H+ influx, thus contributing to cytosolic pH homeostasis by directly modulating H+ flux across the plasma membrane. The fact that some AMTs/NRTs mediate H+-coupled substrate influx, whereas other intra-family members facilitate H+-uncoupled substrate transport, demonstrates that not all plasma membrane transporters possess H+-coupled substrate transport mechanisms, and using the transport mechanism of a protein to represent the case of the entire family is not suitable. The transport activity of these proteins is regulated by extracellular and/or cytosolic pH, with different structural bases for H+ transfer among these seven types of proteins. Notably, intra-family members possess distinct pH regulatory characterization and underlying residues for H+ transfer. This review is anticipated to facilitate the understanding of the molecular basis for cytosolic pH homeostasis. Despite this progress, the strategy of their cooperation for cytosolic pH homeostasis needs further investigation.

A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces.

Water-assisted proton transport through confined spaces influences many phenomena in biomolecular and nanomaterial systems. In such cases, the water molecules that fluctuate in the confined pathways provide the environment and the medium for the hydrated excess proton migration via Grotthuss shuttling. However, a definitive collective variable (CV) that accurately couples the hydration and the connectivity of the proton wire with the proton translocation has remained elusive. To address this important challenge-and thus to define a quantitative paradigm for facile proton transport in confined spaces-a CV is derived in this work from graph theory, which is verified to accurately describe water wire formation and breakage coupled to the proton translocation in carbon nanotubes and the Cl-/H+ antiporter protein, ClC-ec1. Significant alterations in the conformations and thermodynamics of water wires are uncovered after introducing an excess proton into them. Large barriers in the proton translocation free-energy profiles are found when water wires are defined to be disconnected according to the new CV, even though the pertinent confined space is still reasonably well hydrated and-by the simple measure of the mere existence of a water structure-the proton transport would have been predicted to be facile via that oversimplified measure. In this paradigm, however, the simple presence of water is not sufficient for inferring proton translocation, since an excess proton itself is able to drive hydration, and additionally, the water molecules themselves must be adequately connected to facilitate any successful proton transport.

Dense intracellular ion pools in unicellular organisms.

Uptake and concentration of inorganic ions are part of the complex cellular processes required for cell homeostasis, as well as for mineral formation by organisms. These ion transport mechanisms include distinct cellular compartments and chemical phases that play various roles in the physiology of organisms. Here, the prominent cases of dense ion pools in unicellular organisms are briefly reviewed. The specific observations that were reported for different organisms are consolidated into a wide perspective that emphasizes general traits. It is suggested that the intracellular ion pools can be divided into three types: a high cytoplasmic concentration, a labile storage compartment that hosts dense ion-rich phases, and a mineral-forming compartment in which a stable long-lived structure is formed. Recently, many labile pools were identified in various organisms using advanced techniques, bringing many new questions about their possible roles in the formation of the stable mineralized structures.

Mathematical model reveals that heterogeneity in the number of ion transporters regulates the fraction of mouse sperm capacitation.

Capacitation is a complex maturation process mammalian sperm must undergo in the female genital tract to be able to fertilize an egg. This process involves, amongst others, physiological changes in flagellar beating pattern, membrane potential, intracellular ion concentrations and protein phosphorylation. Typically, in a capacitation medium, only a fraction of sperm achieve this state. The cause for this heterogeneous response is still not well understood and remains an open question. Here, one of our principal results is to develop a discrete regulatory network, with mostly deterministic dynamics in conjunction with some stochastic elements, for the main biochemical and biophysical processes involved in the early events of capacitation. The model criterion for capacitation requires the convergence of specific levels of a select set of nodes. Besides reproducing several experimental results and providing some insight on the network interrelations, the main contribution of the model is the suggestion that the degree of variability in the total amount and individual number of ion transporters among spermatozoa regulates the fraction of capacitated spermatozoa. This conclusion is consistent with recently reported experimental results. Based on this mathematical analysis, experimental clues are proposed for the control of capacitation levels. Furthermore, cooperative and interference traits that become apparent in the modelling among some components also call for future theoretical and experimental studies.

Arbuscular mycorrhizal symbioses alleviating salt stress in maize is associated with a decline in root-to-leaf gradient of Na+/K+ ratio.

BACKGROUND: Inoculation of arbuscular mycorrhizal (AM) fungi has the potential to alleviate salt stress in host plants through the mitigation of ionic imbalance. However, inoculation effects vary, and the underlying mechanisms remain unclear. Two maize genotypes (JD52, salt-tolerant with large root system, and FSY1, salt-sensitive with small root system) inoculated with or without AM fungus Funneliformis mosseae were grown in pots containing soil amended with 0 or 100 mM NaCl (incrementally added 32 days after sowing, DAS) in a greenhouse. Plants were assessed 59 DAS for plant growth, tissue Na+ and K+ contents, the expression of plant transporter genes responsible for Na+ and/or K+ uptake, translocation or compartmentation, and chloroplast ultrastructure alterations. RESULTS: Under 100 mM NaCl, AM plants of both genotypes grew better with denser root systems than non-AM plants. Relative to non-AM plants, the accumulation of Na+ and K+ was decreased in AM plant shoots but increased in AM roots with a decrease in the shoot: root Na+ ratio particularly in FSY1, accompanied by differential regulation of ion transporter genes (i.e., ZmSOS1, ZmHKT1, and ZmNHX). This induced a relatively higher Na+ efflux (recirculating) rate than K+ in AM shoots while the converse outcoming (higher Na+ influx rate than K+) in AM roots. The higher K+: Na+ ratio in AM shoots contributed to the maintenance of structural and functional integrity of chloroplasts in mesophyll cells. CONCLUSION: AM symbiosis improved maize salt tolerance by accelerating Na+ shoot-to-root translocation rate and mediating Na+/K+ distribution between shoots and roots.