Cellular Sodium Research Articles

Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: Guardians against Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Heart Diseases.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an innovative class of antidiabetic drugs that provide cardiovascular benefits to both diabetic and nondiabetic patients, surpassing those of other antidiabetic drugs. Although the roles of mitochondria and endoplasmic reticulum (ER) in cardiovascular research are increasingly recognized as promising therapeutic targets, the exact molecular mechanisms by which SGLT2 inhibitors influence mitochondrial and ER homeostasis in the heart remain incompletely elucidated. This review comprehensively summarizes and discusses the impacts of SGLT2 inhibitors on mitochondrial dysfunction and ER stress in heart diseases including heart failure, ischemic heart disease/myocardial infarction, and arrhythmia from preclinical and clinical studies. Based on the existing evidence, the effects of SGLT2 inhibitors may potentially involve the restoration of mitochondrial biogenesis and alleviation of ER stress. Such consequences are achieved by enhancing adenosine triphosphate (ATP) production, preserving mitochondrial membrane potential, improving the activity of electron transport chain complexes, maintaining mitochondrial dynamics, mitigating oxidative stress and apoptosis, influencing cellular calcium and sodium handling, and targeting the unfolded protein response (UPR) through three signaling pathways including inositol requiring enzyme 1α (IRE1α), protein kinase R like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6). Therefore, SGLT2 inhibitors have emerged as a promising target for treating heart diseases due to their potential to improve mitochondrial functions and ER stress.

A root cap-localized NAC transcription factor controls root halotropic response to salt stress in Arabidopsis

Plants are capable of altering root growth direction to curtail exposure to a saline environment (termed halotropism). The root cap that surrounds root tip meristematic stem cells plays crucial roles in perceiving and responding to environmental stimuli. However, how the root cap mediates root halotropism remains undetermined. Here, we identified a root cap-localized NAC transcription factor, SOMBRERO (SMB), that is required for root halotropism. Its effect on root halotropism is attributable to the establishment of asymmetric auxin distribution in the lateral root cap (LRC) rather than to the alteration of cellular sodium equilibrium or amyloplast statoliths. Furthermore, SMB is essential for basal expression of the auxin influx carrier gene AUX1 in LRC and for auxin redistribution in a spatiotemporally-regulated manner, thereby leading to directional bending of roots away from higher salinity. Our findings uncover an SMB-AUX1-auxin module linking the role of the root cap to the activation of root halotropism.

A DNA nanodevice for mapping sodium at single-organelle resolution.

Cellular sodium ion (Na+) homeostasis is integral to organism physiology. Our current understanding of Na+ homeostasis is largely limited to Na+ transport at the plasma membrane. Organelles may also contribute to Na+ homeostasis; however, the direction of Na+ flow across organelle membranes is unknown because organellar Na+ cannot be imaged. Here we report a pH-independent, organelle-targetable, ratiometric probe that reports lumenal Na+. It is a DNA nanodevice containing a Na+-sensitive fluorophore, a reference dye and an organelle-targeting domain. By measuring Na+ at single endosome resolution in mammalian cells and Caenorhabditis elegans, we discovered that lumenal Na+ levels in each stage of the endolysosomal pathway exceed cytosolic levels and decrease as endosomes mature. Further, we find that lysosomal Na+ levels in nematodes are modulated by the Na+/H+ exchanger NHX-5 in response to salt stress. The ability to image subcellular Na+ will unveil mechanisms of Na+ homeostasis at an increased level of cellular detail.

Preliminary pharmacokinetic and safety data after a single intravenous infusion of Voyager-V1 (VV1, VSV-IFNβ-NIS) oncolytic virus in patients with relapsed refractory hematologic malignancies.

e14594 Background: Voyager-V1 (VV1) is an oncolytic vesicular stomatitis virus engineered to express interferon beta (IFNβ) to boost cellular antitumor immunity and sodium iodine symporter (NIS). A phase 1 trial investigating a single infusion of VV1 in patients with relapsed refractory multiple myeloma and T-cell lymphoma (TCL) showed promising and durable clinical activity, primarily in patients with TCL. VV1 infects tumor cells and macrophages in the lymph nodes and spleen, resulting in release of tumor antigens and IFNβ that activates and boost cellular antitumor immunity. We present the preliminary pharmacokinetic analysis in patients given one intravenous (IV) dose of VV1. Methods: Patients received 5e9 to 1.7e11 TCID50 (50% tissue culture infective dose) of VV1 given over 30 minutes. We also explored the impact of infusion duration (0.25, 0.5,1 and 3 hours) in 17 patients with solid tumors. The objectives were to determine the impact of viral dose on pharmacokinetics (PK) of VSV and IFNβ. For VSV and IFNβ PK, whole blood was collected in 30 patients on days 1, 2, 3, and 8. Dose levels were 1.7E10, 5E10, and 1.7E11 TCID50. The plasma concentration-time data were estimated with non-compartmental analysis using WinNonlin 8.3. Results: The half-life of VV1 is comparable (10-12h) between dose levels of 1.7e10, 5e10 and 1.7e11. Ideal infusion rate was found to be 30 minutes and provides the highest Cmax and AUC. Most peak concentrations for viremia and IFNβ were achieved between ‘end of infusion’ and 2.5 hours, 4.5 and 24 hours, respectively. Following infusion, a second concentration peak is found in over half the patients leading to highly variable terminal elimination half-life, specifically where the second peak is at 24 hours. There was no second peak for IFNβ levels. Peak plasma concentration and systemic exposure increased in proportion to increased dose, consistent with linear clearance. Conclusions: The 30 minute infusion rate was considered the best as its PK provides the highest Cmax and AUC with no significant CRS differences among other groups. IL-6 and IFNα markers at hour 4 indicate a likely CRS and hour 24 provides a possible prediction of the grade. Cmax and AUC were also highest at 1.7e11 TCID50. This is the recommended dose that will be used in the expansion arm in patients with TCL. Clinical trial information: NCT03017820 , NCT02923466 . [Table: see text]

Effect of sodium channels in Alzheimer’s disease

Alzheimer disease (AD), depicted by the formation of amyloid β-protein plaque(Aβ), has been recognized for dementia and epilepsy. The pathological mechanism of AD is complicated and it remains unclear. Currently, most therapies are focusing on elimination of Aβ plaque and preventing the breakdown of acetylcholine to prevent neuron cell death, however, most of these drugs fail to improve cognitive functions in AD patients. Therefore, the development of novel therapies for AD is in urgent need. Emerging evidences show that cellular sodium (Na+) signals play a significant role in neurol physiology. Aβ oligomer upregulates the expression of Nav1.6, leading to cognition loss, epilepsy, and malfunction of neuron development (shorter neurite length is observed during Aβ-interfered neuron development), indicating that sodium channel may be a target for treating AD. This review summarizes current development of molecular mechanisms linking sodium dysregulation with AD pathologies and discusses potential therapies for AD by correcting Na+ disruption.

Impact of the muscular Training on the levels of Sodium and Potassium and on the activity of lactate dehydrogenase in blood serum

The recent study aimed at evaluating the impact of the training intensity and the muscular stress the activity of (Na+ - K – ATP ase). The levels of the extra cellular (Sodium and Potassium) (blood serum) and the activity of the lactate dehydrogenase were evaluated for the handball players before and after exercising the sport training as well as evaluated the same data for the basketball players (The most stressed in training) before and after exercising these special game trainings. The research samples were gathered from (30) players of handball and basketball.
 The blood serum isolated to perform the required tests by using the special kits of each test.
 The results of measuring the extra cellular sodium showed a significant decrease (P≤ 0.05) for the handball players after exercising the sport training compared with the concentration before exercising the training. As well as the case of basketball players , the study results indicated that the sodium concentrations (P≤ 0.05) decreased significantly after exercising the sport training compared with the concentration before exercising the training. These results also showed the significant differences (P≤ 0.05) in comparison with the two player groups of handball and basketball before and after exercising the training.
 As to the concentration of extra cellular potassium the results appeared a significant increase (P≤ 0.05) for the handball players after exercising the sport training compared with the concentration before exercising the training. As well as the case of basketball players , the results of study showed a significant increase at potassium concentration (P≤ 0.05) after exercising the sport training compared with the concentration before training. The results also appeared the absence of significant differences in comparison with the two – player groups before trainings. In comparison with potassium concentration after training between the two groups , the results gave significant different (P≤ 0.05) in which potassium was more concentrated in basketball group.
 As to the lactate dehydrogenase activity , the results showed a significant increase in enzyme activity (P≤ 0.05) in the two – players groups after the training , but there were no significant differences in comparison with the both player groups of handball and basketball after performing the trainings.
 This indicated to occurring changes in activity of (Na+ - K ATP ase) in case of happening the body stress , leading to decrease in concentration of extra cellular sodium and increase in concentration of extra cellular potassium and then followed some changes at level of these elements intra cellular. So this change increased with increasing the stress intensity.

Nanomaterial-modulated cellular sodium extrusion and vacuolar sequestration for salt tolerance

Nanomaterials can induce plant tolerance to abiotic environmental stresses, whereas the sensing mechanism and the resulting response at the cellular level need further exploration.

Biodegradation of Synthetic Pyrethroid Insecticide Deltamethrin by Stenotrophomonas maltophilia Strain DRNB1

: Deltamethrin is one of the most used pyrethroid insecticide in different regions of the world. It is the fastacting insecticide that disrupts the cellular sodium channels. The deltamethrin residues are highly retained in environments, particularly in soil and water and have inevitable side effects on natural resources and human health. The most efficient, economical, and environmentally beneficial way of removing deltamethrin from contaminated sites is bioremediation. Bacteria are the most used biological agents in biodegradation studies. Thus, in this study deltamethrin-degrading bacteria Stenotrophomonas maltophilia strain DRNB1 was isolated and characterised. The bacterial growth was analysed by UV-spectrophotometer and deltamethrin degradation was studied by GC-MS analysis. S. maltophilia strain DRNB1 used deltamethrin as the sole carbon source for growth. Deltamethrin degradation efficiency of DRNB1 was 89.2% in insecticide supplemented media and 93% in presence of additional glucose in mineral media. These results implies that S. maltophilia strain DRNB1 could be used as a bioremediation technology for deltamethrin contaminated environments.

Cellular Size, Gap Junctions, and Sodium Channel Properties Govern Developmental Changes in Cardiac Conduction.

Electrical conduction in cardiac ventricular tissue is regulated via sodium (Na+) channels and gap junctions (GJs). We and others have recently shown that Na+channels preferentially localize at the site of cell-cell junctions, the intercalated disc (ID), in adult cardiac tissue, facilitating coupling via the formation of intercellular Na+nanodomains, also termed ephaptic coupling (EpC). Several properties governing EpC vary with age, including Na+channel and GJ expression and distribution and cell size. Prior work has shown that neonatal cardiomyocytes have immature IDs with Na+channels and GJs diffusively distributed throughout the sarcolemma, while adult cells have mature IDs with preferentially localized Na+channels and GJs. In this study, we perform an in silico investigation of key age-dependent properties to determine developmental regulation of cardiac conduction. Simulations predict that conduction velocity (CV) biphasically depends on cell size, depending on the strength of GJ coupling. Total cell Na+channel conductance is predictive of CV in cardiac tissue with high GJ coupling, but not correlated with CV for low GJ coupling. We find that ephaptic effects are greatest for larger cells with low GJ coupling typically associated with intermediate developmental stages. Finally, simulations illustrate how variability in cellular properties during different developmental stages can result in a range of possible CV values, with a narrow range for both neonatal and adult myocardium but a much wider range for an intermediate developmental stage. Thus, we find that developmental changes predict associated changes in cardiac conduction.

Cryo-EM structure of the sodium-driven chloride/bicarbonate exchanger NDCBE

SLC4 transporters play significant roles in pH regulation and cellular sodium transport. The previously solved structures of the outward facing (OF) conformation for AE1 (SLC4A1) and NBCe1 (SLC4A4) transporters revealed an identical overall fold despite their different transport modes (chloride/bicarbonate exchange versus sodium-carbonate cotransport). However, the exact mechanism determining the different transport modes in the SLC4 family remains unknown. In this work, we report the cryo-EM 3.4 Å structure of the OF conformation of NDCBE (SLC4A8), which shares transport properties with both AE1 and NBCe1 by mediating the electroneutral exchange of sodium-carbonate with chloride. This structure features a fully resolved extracellular loop 3 and well-defined densities corresponding to sodium and carbonate ions in the tentative substrate binding pocket. Further, we combine computational modeling with functional studies to unravel the molecular determinants involved in NDCBE and SLC4 transport.

Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.

Cardiac glycosides are natural sterols and constitute a group of secondary metabolites isolated from plants and animals. These cardiotonic agents are well recognized and accepted in the treatment of various cardiac diseases as they can increase the rate of cardiac contractions by acting on the cellular sodium potassium ATPase pump. However, a growing number of recent efforts were focused on exploring the antitumor and antiviral potential of these compounds. Several reports suggest their antitumor properties and hence, today cardiac glycosides (CG) represent the most diversified naturally derived compounds strongly recommended for the treatment of various cancers. Mutated or dysregulated transcription factors have also gained prominence as potential therapeutic targets that can be selectively targeted. Thus, we have explored the recent advances in CGs mediated cancer scope and have considered various signaling pathways, molecular aberration, transcription factors (TFs), and oncogenic genes to highlight potential therapeutic targets in cancer management.

Precision Targeting of Ion Channel Blocker for the Treatment of AML

The survival rate of patients with acute myeloid leukemia (AML) remains modest and thus, there is a clear need for advanced treatments. Here we describe two drug leads for AML that inhibit cellular sodium release without requiring drug internalization. EDC1 and EDC8 are two very potent extracellular antibody drug conjugates that selectively inhibit the all-important Na,K-ATPase, an ion pump required by cells to export excess sodium and to maintain ion gradients needed to import and export many important nutrients and waste products. We first demonstrate that dysadherin (a known metastatic cancer marker), is expressed on the surface many types of AML cell lines and can be used to direct Na,K-ATPase inhibitors using EDC1. We next demonstrate that ATRA inducible AML cells types are selectively destroyed with Na,K-ATPase inhibitors targeted to CD38 using EDC8 and ATRA.Since dysadherin expression is a known to be correlated to metastasis and stemness but yet to be studied in AML, we first analyzed a number of leukemia cell lines and AML patient samples for dysadherin expression by analyzing their surface expression and/or their sensitivity to EDC1. We observed that many cultured AML cells express dysadherin and are sensitive to EDC1 with EC50 values ranged from 0.02 to 1.0 nanoMolar and cell viability after 72 hours of exposure ranging from zero to 10%. For the three primary AML patient specimens analyzed, dysadherin expression was seen. Interestingly, in two of these three samples, the majority of intense staining was found in the CD123+ CD34+ population.Since CD38 expression and inducible expression can now be diagnosed in patients with AML, we analyzed if ATRA was required to sensitize AML to EDC8. Using multiple leukemic cell lines (HL60, U937, MV411, KG1, K562, and OCI/AML3) known to express CD38 with or without requiring ATRA, we analyzed EDC8 sensitivity before and after ATRA addition. We found that CD38 expression was required for EDC8 sensitivity and once expressed, EDC8 displayed potent activity with few viable cells detectable.Further studies analyzing dysadherin and CD38 expression in patient samples are needed to better understand the AML cell populations that may be affected by these EDCs but these results show the potential of this new type of antibody drug conjugate technology for the treatment of AML. EDCs that inhibit a required membrane bound ion pump with the precision of antibodies without requiring internalization may provide a new tool for doctors in their fight against AML. DisclosuresMarshall:CENTROSE: Employment. Malavasi:Jaansen Pharmaceuticals: Research Funding. Prudent:CENTROSE: Employment, Equity Ownership.

NFAT5 Is Involved in GRP-Enhanced Secretion of GLP-1 by Sodium.

Gastrin, secreted by G-cells, and glucagon-like peptide-1 (GLP-1), secreted by L-cells, may participate in the regulation of sodium balance. We studied the effect of sodium in mice in vivo and mouse ileum and human L-cells, on GLP-1 secretion, and the role of NFAT5 and gastrin-releasing peptide receptor (GRPR) in this process. A high-sodium diet increases serum GLP-1 levels in mice. Increasing sodium concentration stimulates GLP-1 secretion from mouse ileum and L-cells. GRP enhances the high sodium-induced increase in GLP-1 secretion. High sodium increases cellular GLP-1 expression, while low and high sodium concentrations increase NFAT5 and GRPR expression. Silencing NFAT5 in L-cells abrogates the stimulatory effect of GRP on the high sodium-induced GLP-1 secretion and protein expression, and the sodium-induced increase in GRPR expression. GLP-1 and gastrin decrease the expression of Na+-K+/ATPase and increase the phosphorylation of sodium/hydrogen exchanger type 3 (NHE3) in human renal proximal tubule cells (hRPTCs). This study gives a new perspective on the mechanisms of GLP-1 secretion, especially that engendered by ingested sodium, and the ability of GLP-1, with gastrin, to decrease Na+-K+/ATPase expression and NHE3 function in hRPTCs. These results may contribute to the better utilization of current and future GLP-1-based drugs in the treatment of hypertension.

Nano-fertilizers and their impact on vegetables: Contribution of Nano-chelate Super Plus ZFM and Lithovit®-standard to improve salt-tolerance of pepper

The implementation of nano-technology for the amelioration of plant tolerance against abiotic stress has been widely reported in last years. In the current study, the separate and combined effects of Nano-chelate Super Plus ZFM (A) and Lithovit®-standard (B) on salt-stressed chili pepper were evaluated. Two different concentrations of each products were tested (A1, 2.5 g L−1, A2, 5 g L−1; B1, 3 g L−1 and B2, 5 g L−1) on pepper irrigated by three NaCl solutions (1.5dS m−1, 3dS m−1 and 6dS m−1. The control (no treatment) experiments were only irrigated with the three NaCl solutions. Spraying Nano-chelate Super Plus ZFM in low concentration (A1) enhanced significantly iron, zinc and manganese content in shoots and fruits. The application of Lithovit®-standard at high concentration ameliorated calcium and magnesium content in plant parts. A1B2 caused the highest enhancement in leaf number, fresh and dry weights of plant parts. It also improved fruit number significantly, fruit fresh and dry weight, yield plant−1 and fruit dimension compared to control under all NaCl solutions. All treatments improved carotenoids content and reduced cellular electrolyte leakage and sodium content, as compared to control. Low concentration of Nano-chelate Super Plus ZFM improved chlorophyll a (Chl a), b (Chl b) and total chlorophyll (TChl) more than the high concentration (A2). Photosynthetic pigments were maximized by A1B2. Treating plants with A1B2 and A1B1 improved the most nitrogen and potassium content respectively in shoots and fruits compared to control at all EC levels. Combining both products would be an efficient method inducing salt-tolerance of pepper.

Activity-Regulated Cytoskeleton-Associated Protein (Arc/Arg3.1) is Transiently Expressed after Heat Shock Stress and Suppresses Heat Shock Factor 1

Heat shock proteins are induced by activation of heat shock factor 1 (HSF1) in response to heat shock and protect against heat stress. However, the molecular mechanisms underlying the downstream signal of heat shock have not been fully elucidated. We found that similarly to canonical Hsps, Arc/Arg3.1 is also markedly induced by heat shock and by other cellular stress inducers, including diamide, sodium arsenite and H2O2 in various cells. We noted that heat stress–induced Arc/Arg3.1 protein is short lived, with a half-life of <30 min, and is readily degraded by the ubiquitin–proteasome system. Arc/Arg3.1 overexpression inhibited the up-regulation of heat shock–induced Hsp70 and Hsp27, suggesting that Arc/Arg3.1 is a negative regulator of heat shock response (HSR). Studying the effect of Arc/Arg3.1 on HSF1, a major transcription factor in HSR, we found that Arc/Arg3.1 binds to HSF1 and inhibits its binding to the heat shock element in gene promoters, resulting in reduced induction of Hsp27 and Hsp70 mRNAs, without affecting HSF1′s phosphorylation-dependent activation, or nuclear localization. Arc/Arg3.1 overexpression decreased cell survival in response to heat shock. We conclude that Arc/Arg3.1 is transiently expressed after heat shock and negatively regulates HSF1 in the feedback loop of HSR.

Visualizing cellular sodium hydrosulfite (Na2S2O4) using azo-based fluorescent probes with a high signal-to-noise ratio.

Developing a reliable method to detect Na2S2O4 in real time is of great importance for the in-depth study of its toxicity to humans and to allow it to be safely handled. Currently, research on the fluorescence imaging of Na2S2O4 is very scarce. Herein, we present azo-based turn-on fluorescent probes with a high signal-to-noise ratio (emission enhancement >100-fold) for the visualization of Na2S2O4 in living cells.

Generation and Characterization of a Neutralizing Human Monoclonal Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library.

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity (KD) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

Reverse NCX Attenuates Cellular Sodium Loading in Metabolically Compromised Cortex.

In core regions of ischemic stroke, disruption of blood flow causes breakdown of ionic gradients and, ultimately, calcium overload and cell death. In the surrounding penumbra, cells may recover upon reperfusion, but recovery is hampered by additional metabolic demands imposed by peri-infarct depolarizations (PIDs). There is evidence that sodium influx drives PIDs, but no data exist on PID-related sodium accumulations in vivo. Here, we found that PIDs in mouse neocortex are associated with propagating sodium elevations in neurons and astrocytes. Similar transient sodium elevations were induced in acute tissue slices by brief chemical ischemia. Blocking NMDA-receptors dampened sodium and accompanying calcium loads of neurons in tissue slices, while inhibiting glutamate transport diminished sodium influx into astrocytes, but amplified neuronal sodium loads. In both cell types, inhibition of sodium/calcium exchange (NCX) increased sodium transients. Blocking NCX also significantly reduced calcium transients, a result confirmed in vivo. Our study provides the first quantitative data on sodium elevations in peri-infarct regions in vivo. They suggest that sodium influx drives reversal of NCX, triggering a massive secondary calcium elevation while promoting export of sodium. Reported neuroprotective effects of NCX activity in stroke models might thus be related to its dampening of ischemia-induced sodium loading.

Enhanced sodium acetate tolerance in Saccharomyces cerevisiae by the Thr255Ala mutation of the ubiquitin ligase Rsp5.

Sodium and acetate inhibit cell growth and ethanol fermentation by different mechanisms in Saccharomyces cerevisiae. We identified the substitution of a conserved Thr255 to Ala (T255A) in the essential Nedd4-family ubiquitin ligase Rsp5, which enhances cellular sodium acetate tolerance. The T255A mutation selectively increased the resistance of cells against sodium acetate, suggesting that S. cerevisiae cells possess an Rsp5-mediated mechanism to cope with the composite stress of sodium and acetate. The sodium acetate tolerance was dependent on the extrusion of intracellular sodium ions by the plasma membrane-localized sodium pumps Ena1, Ena2, and Ena5 (Ena1/2/5) and two known upstream regulators: the Rim101 pH signaling pathway and the Hog1 mitogen-activated protein kinase. However, the T255A mutation affected neither the ubiquitination level of the Rsp5 adaptor protein Rim8 nor the phosphorylation level of Hog1. These data raised the possibility that Rsp5 enhances the function of Ena1/2/5 specifically in response to sodium acetate through an unknown mechanism other than ubiquitination of Rim8 and activation of Hog1-mediated signaling. Also, an industrial yeast strain that expresses the T255A variant exhibited increased initial fermentation rates in the presence of sodium acetate. Hence, this mutation has potential for the improvement of bioethanol production from lignocellulosic biomass.

Selection and functional analysis of a Pyropia yezoensis ammonium transporter PyAMT1 in potassium deficiency

Seaweeds are believed to have developed unique mechanisms to maintain optimal cellular potassium and sodium concentrations in order to survive in the saline marine environment. To gain a molecular understanding of underlying potassium/sodium homeostasis in seaweeds, full-length cDNA libraries from the multiple stages in the life cycle, including gametophytes, conchosporangia and sporophytes of a marine red alga, Pyropia yezoensis, were constructed. A large portion of genes from each library through the life cycle was revealed to be functionally unknown reconfirming the uniqueness of P. yezoensis genes in terms of evolutionary lineage. Genes that could potentially contribute to potassium deficiency tolerance were selected from the potassium uptake defective Escherichia coli strain expressing gametophytes and conchosporangia libraries under the low potassium conditions. Of those, an ammonium transporter gene, PyAMT1, was demonstrated to enhance potassium deficiency tolerance effectively when expressed in the E. coli strain. Potential roles of PyAMT1 and other candidate components in this context are discussed.