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Traffic (Copenhagen, Denmark) Jan 2024Ceroid lipofuscinosis neuronal 5 (CLN5) and cathepsin D (CTSD) are soluble lysosomal enzymes that also localize extracellularly. In humans, homozygous mutations in CLN5...
Ceroid lipofuscinosis neuronal 5 (CLN5) and cathepsin D (CTSD) are soluble lysosomal enzymes that also localize extracellularly. In humans, homozygous mutations in CLN5 and CTSD cause CLN5 disease and CLN10 disease, respectively, which are two subtypes of neuronal ceroid lipofuscinosis (commonly known as Batten disease). The mechanisms regulating the intracellular trafficking of CLN5 and CTSD and their release from cells are not well understood. Here, we used the social amoeba Dictyostelium discoideum as a model system to examine the pathways and cellular components that regulate the intracellular trafficking and release of the D. discoideum homologs of human CLN5 (Cln5) and CTSD (CtsD). We show that both Cln5 and CtsD contain signal peptides for secretion that facilitate their release from cells. Like Cln5, extracellular CtsD is glycosylated. In addition, Cln5 release is regulated by the amount of extracellular CtsD. Autophagy induction promotes the release of Cln5, and to a lesser extent CtsD. Release of Cln5 requires the autophagy proteins Atg1, Atg5, and Atg9, as well as autophagosomal-lysosomal fusion. Atg1 and Atg5 are required for the release of CtsD. Together, these data support a model where Cln5 and CtsD are actively released from cells via their signal peptides for secretion and pathways linked to autophagy. The release of Cln5 and CtsD from cells also requires microfilaments and the D. discoideum homologs of human AP-3 complex mu subunit, the lysosomal-trafficking regulator LYST, mucopilin-1, and the Wiskott-Aldrich syndrome-associated protein WASH, which all regulate lysosomal exocytosis in this model organism. These findings suggest that lysosomal exocytosis also facilitates the release of Cln5 and CtsD from cells. In addition, we report the roles of ABC transporters, microtubules, osmotic stress, and the putative D. discoideum homologs of human sortilin and cation-independent mannose-6-phosphate receptor in regulating the intracellular/extracellular distribution of Cln5 and CtsD. In total, this study identifies the cellular mechanisms regulating the release of Cln5 and CtsD from D. discoideum cells and provides insight into how altered trafficking of CLN5 and CTSD causes disease in humans.
Topics: Humans; Neuronal Ceroid-Lipofuscinoses; Cathepsin D; Dictyostelium; Protein Sorting Signals; Lysosomal Membrane Proteins
PubMed: 38272448
DOI: 10.1111/tra.12925 -
Nutrients Nov 2023The effects of varying sodium (Na) and carbohydrate (CHO) in oral rehydration solutions (ORS) and sports drinks (SD) for rehydration following exercise are unclear. We... (Randomized Controlled Trial)
Randomized Controlled Trial
The effects of varying sodium (Na) and carbohydrate (CHO) in oral rehydration solutions (ORS) and sports drinks (SD) for rehydration following exercise are unclear. We compared an ORS and SD for the percent of fluid retained (%FR) following exercise-induced dehydration and hypothesized a more complete rehydration for the ORS (45 mmol Na/L and 2.5% CHO) and that the %FR for the ORS and SD (18 mmol Na/L and 6% CHO) would exceed the water placebo (W). A placebo-controlled, randomized, double-blind clinical trial was conducted. To induce 2.6% body mass loss (BML, > 0.05 between treatments), 26 athletes performed three 90 min interval training sessions without drinking fluids. Post-exercise, participants replaced 100% of BML and were observed for 3.5 h for the %FR. Mean ± SD for the %FR at 3.5 h was 58.1 ± 12.6% (W), 73.9 ± 10.9% (SD), and 76.9 ± 8.0% (ORS). The %FR for the ORS and SD were similar and greater than the W ( < 0.05 ANOVA and Tukey HSD). Two-way ANOVA revealed a significant interaction with the ORS having greater suppression of urine production in the first 60 min vs. W (SD did not differ from W). By 3.5 h, the ORS and SD promoted greater rehydration than did W, but the pattern of rehydration early in recovery favored the ORS.
Topics: Humans; Sodium; Fluid Therapy; Water-Electrolyte Balance; Beverages; Carbohydrates; Athletes; Dehydration
PubMed: 38004153
DOI: 10.3390/nu15224759 -
Journal of Trace Elements in Medicine... Sep 2023Different anthropogenic activities as well as natural sources contribute enormously towards various heavy metal contaminations in aquatic habitats. Cadmium (Cd) is one... (Review)
Review
Different anthropogenic activities as well as natural sources contribute enormously towards various heavy metal contaminations in aquatic habitats. Cadmium (Cd) is one of most prevalent and toxic heavy metals with a long half life. Unlike terrestrial animals, exposure of Cd in fishes may happen not only through feeds but also from its habitat water. Bioaccumulation of Cd in fishes occurs in many tissues, but mainly in gill, liver, kidney, skin, and muscle. The concentrations of Cd in fish tissues depend upon the extent and duration of Cd exposure, species and age of fishes, dietary minerals and antioxidant concentrations, and habitat water quality. Specific histopathological observations in liver, kidney, and gill are useful to understand the effects of Cd, which could help to determine the ameliorating methods to be adopted. Exposure of Cd exerts several adverse effects on general growth and development, reproductive processes, osmoregulation, morphological and histological structures, stress tolerance, and endocrine system, mainly due to changes in biological functions induced by differential expressions of several genes related to oxidative stress, apoptosis, inflammation, immunosuppressions, genotoxicity, Cd chelation and carbohydrate metabolism. Chronic biomagnifications of Cd exceeding the permitted level may be harmful not only to the fishes itself but also to humans through food chains. Amelioration of such toxic heavy metal that has been categorized as a potent carcinogenic in humans is of utmost importance. Main modes of amelioration encompas reducing oxidative damages by promoting the antioxidative defenses, decreasing Cd absorption, increasing excretion through excretory system and improving the tolerance of fishes to Cd toxicity. Many amelioration measures such as use of minerals (for example, zinc, calcium, and iron), vitamins (vitamin C, A, and E), different herbs, probiotics and other agents (taurine, bentonite, chitosan, zeolite, and metallothionein) have been explored for their effective roles to reduce Cd bioaccumulation and toxicity symptoms in fishes. The present review discusses bioaccumulation of Cd, histopathological alterations, oxidative stress, synergism-antagonism, and gene regulation in different tissues, and its amelioration measures in fishes.
Topics: Animals; Humans; Cadmium; Bioaccumulation; Water Pollutants, Chemical; Metals, Heavy; Fishes; Antioxidants; Minerals; Heavy Metal Poisoning
PubMed: 37263063
DOI: 10.1016/j.jtemb.2023.127202 -
Seminars in Cell & Developmental Biology Mar 2024Stomatal conductance (g) determines CO uptake for photosynthesis (A) and water loss through transpiration, which is essential for evaporative cooling and maintenance of... (Review)
Review
Stomatal conductance (g) determines CO uptake for photosynthesis (A) and water loss through transpiration, which is essential for evaporative cooling and maintenance of optimal leaf temperature as well as nutrient uptake. Stomata adjust their aperture to maintain an appropriate balance between CO uptake and water loss and are therefore critical to overall plant water status and productivity. Although there is considerable knowledge regarding guard cell (GC) osmoregulation (which drives differences in GC volume and therefore stomatal opening and closing), as well as the various signal transduction pathways that enable GCs to sense and respond to different environmental stimuli, little is known about the signals that coordinate mesophyll demands for CO. Furthermore, chloroplasts are a key feature in GCs of many species, however, their role in stomatal function is unclear and a subject of debate. In this review we explore the current evidence regarding the role of these organelles in stomatal behaviour, including GC electron transport and Calvin-Benson-Bassham (CBB) cycle activity as well as their possible involvement correlating g and A along with other potential mesophyll signals. We also examine the roles of other GC metabolic processes in stomatal function.
Topics: Carbon Dioxide; Photosynthesis; Cell Physiological Phenomena; Biological Transport; Water
PubMed: 36894379
DOI: 10.1016/j.semcdb.2023.03.001 -
Journal of Experimental Zoology. Part... Jan 2024Decapods occupy all aquatic, and terrestrial and semi-terrestrial environments. According to their osmoregulatory capacity, they can be osmoconformers or osmoregulators... (Review)
Review
Decapods occupy all aquatic, and terrestrial and semi-terrestrial environments. According to their osmoregulatory capacity, they can be osmoconformers or osmoregulators (hypo or hyperegulators). The goal of this study is to gather data available in the literature for aquatic decapods and verify if the rare hyporegulatory capacity of decapods is associated with hyper-regulatory capacity. The metric used to quantify osmoregulation was the osmotic capacity (OC), the gradient between external and internal (hemolymph) osmolalities. We employ phylogenetic comparative methods using 83 species of decapods to test the correlation between hyper OC and hypo OC, beyond the ancestral state for osmolality habitat, which was used to reconstruct the colonization route. Our analysis showed a phylogenetic signal for habitat osmolality, hyper OC and hypo OC, suggesting that hyper-hyporegulators decapods occupy similar habitats and show similar hyper and hyporegulatory capacities. Our findings reveal that all hyper-hyporegulators decapods (mainly shrimps and crabs) originated in estuarine waters. Hyper OC and hypo OC are correlated in decapods, suggesting correlated evolution. The analysis showed that species which inhabit environments with intense salinity variation such as estuaries, supratidal and mangrove habitats, all undergo selective pressure to acquire efficient hyper-hyporegulatory mechanisms, aided by low permeabilities. Therefore, hyporegulation can be observed in any colonization route that passes through environments with extreme variations in salinity, such as estuaries or brackish water.
Topics: Animals; Osmoregulation; Phylogeny; Decapoda; Brachyura; Ecosystem
PubMed: 37853933
DOI: 10.1002/jez.2757 -
Plant Signaling & Behavior Dec 2024Tomato ( L.) is one of the most important economic crops in China. However, its quality and yield are susceptible to the adverse effects of low temperatures. In our...
Tomato ( L.) is one of the most important economic crops in China. However, its quality and yield are susceptible to the adverse effects of low temperatures. In our study, two tomato cultivars, showing different tolerance to low temperatures, namely the cold-sensitive tomato cultivar (S708) and cold-tolerant tomato cultivar (T722), were grown at optimal (25/18°C) and sub-optimal (15/10°C) temperature conditions for 5 days. Our study aimed to explore the effect of sub-optimal temperature on fresh weight, chlorophyll content and chlorophyll fluorescence, soluble sugars and proline content of two tomato cultivars. Moreover, we employed RNA-Seq to analyze the transcriptomic response of tomato roots to sub-optimal temperature. The results revealed that S708 showed a more significant reduction in fresh weight, chlorophyll content, photochemical efficiency of PSII (YII), maximum quantum yield of PSII (Fv/Fm), photochemical quenching (qP) and electron transport rate (ETR) compared to T722 under the sub-optimal temperature condition. Notably, T722 maintained higher level of soluble sugars and proline in comparison to S708 uner sub-optimal temperature. RNA-seq data showed that up-regulated DEGs in both tomato cultivars were involved in "plant-pathogen interaction", "MAPK signaling pathway", "plant hormone signal transduction", and "phosphatidylinositol signaling system". Furthermore, "Amino sugar and nucleotide sugar metabolism" pathway was enriched only in T722. Moreover, under sub-optimal temperature, transcription factor genes and osmoregulation genes showed varying degrees of response in both tomato cultivars. Conclusion: In summary, our results offer detailed insights into the response characteristics of tomato to sub-optimal temperature, providing valuable references for the practical management of tomato crops under sub-optimal temperature condition.
Topics: Temperature; Solanum lycopersicum; Chlorophyll; Proline; Gene Expression Profiling; Sugars; Stress, Physiological; Photosynthesis
PubMed: 38511566
DOI: 10.1080/15592324.2024.2332018 -
Microbiology and Molecular Biology... Mar 2024SUMMARYAcidocalcisomes are organelles conserved during evolution and closely related to the so-called volutin granules of bacteria and archaea, to the... (Review)
Review
SUMMARYAcidocalcisomes are organelles conserved during evolution and closely related to the so-called volutin granules of bacteria and archaea, to the acidocalcisome-like vacuoles of yeasts, and to the lysosome-related organelles of animal species. All these organelles have in common their acidity and high content of polyphosphate and calcium. They are characterized by a variety of functions from storage of phosphorus and calcium to roles in Ca signaling, osmoregulation, blood coagulation, and inflammation. They interact with other organelles through membrane contact sites or by fusion, and have several enzymes, pumps, transporters, and channels.
Topics: Animals; Calcium; Organelles; Polyphosphates; Bacteria; Molecular Biology
PubMed: 38099688
DOI: 10.1128/mmbr.00042-23 -
Deutsche Medizinische Wochenschrift... Feb 2024Osmotic gradients over cell membranes lead to water movement into or out of cells. An intact osmoregulation prevents osmotic gradients, thereby protecting cells from...
Osmotic gradients over cell membranes lead to water movement into or out of cells. An intact osmoregulation prevents osmotic gradients, thereby protecting cells from swelling or shrinking. Na is the major cation in the extracellular fluid (ECF) and the major determinant of the osmolarity in the ECF, including plasma. Therefore, the plasma-Na concentration needs to be tightly regulated. An excess of electrolyte-free water decreases the concentration of osmolytes leading to hyponatremia. In contrast, a free water deficit increases the osmolyte concentration leading to hypernatremia. Pathophysiology-oriented approaches to dysnatremic patients help both clinicians and patients. Therapeutic interventions depend on the differentiation between acute and chronic, asymptomatic, and symptomatic dysnatremia, and on the patient's extracellular volume status. The therapeutic armamentarium for hyponatremia consists of water restriction, hypertonic infusions, urea, V2 receptor-blockers, and sodium-glucose cotransporter 2 (SGLT2) inhibitors. Patients with hypernatremia are treated with electrolyte-free water or hypotonic sodium-containing solutions depending on their volume status. Basic concepts in the management of dysnatremic patients are discussed.
Topics: Humans; Hypernatremia; Hyponatremia; Urea; Water; Sodium
PubMed: 38262402
DOI: 10.1055/a-2055-3486 -
Molecular Omics Sep 2023Drought alone causes more annual loss in crop yield than the sum of all other environmental stresses. There is growing interest in harnessing the potential of...
Drought alone causes more annual loss in crop yield than the sum of all other environmental stresses. There is growing interest in harnessing the potential of stress-resilient PGPR in conferring plant resistance and enhancing crop productivity in drought-affected agroecosystems. A detailed understanding of the complex physiological and biochemical responses will open up the avenues to stress adaptation mechanisms of PGPR communities under drought. It will pave the way for rhizosphere engineering through metabolically engineered PGPR. Therefore, to reveal the physiological and metabolic networks in response to drought-mediated osmotic stress, we performed biochemical analyses and applied untargeted metabolomics to investigate the stress adaptation mechanisms of a PGPR WRS7 ( WRS7). Drought caused oxidative stress and resulted in slower growth rates in WRS7. However, WRS7 could tolerate drought stress and did not show changes in cell morphology under stress conditions. Overproduction of ROS caused lipid peroxidation (increment in MDA) and eventually activated antioxidant systems and cell signalling cascades, which led to the accumulation of ions (Na, K, and Ca), osmolytes (proline, exopolysaccharides, betaine, and trehalose), and modulated lipid dynamics of the plasma membranes for osmosensing and osmoregulation, suggesting an osmotic stress adaption mechanism in PGPR WRS7. Finally, GC-MS-based metabolite profiling and deregulated metabolic responses highlighted the role of osmolytes, ions, and intracellular metabolites in regulating WRS7 metabolism. Our results suggest that understanding the role of metabolites and metabolic pathways can be exploited for future metabolic engineering of PGPR and developing bio inoculants for plant growth promotion under drought-affected agroecosystems.
Topics: Droughts; Plant Development; Enterobacter; Oxidative Stress
PubMed: 37338418
DOI: 10.1039/d3mo00051f -
Current Biology : CB Aug 2023Controlling intracellular osmolarity is essential to all cellular life. Cells that live in hypo-osmotic environments, such as freshwater, must constantly battle water...
Controlling intracellular osmolarity is essential to all cellular life. Cells that live in hypo-osmotic environments, such as freshwater, must constantly battle water influx to avoid swelling until they burst. Many eukaryotic cells use contractile vacuoles to collect excess water from the cytosol and pump it out of the cell. Although contractile vacuoles are essential to many species, including important pathogens, the mechanisms that control their dynamics remain unclear. To identify the basic principles governing contractile vacuole function, we investigate here the molecular mechanisms of two species with distinct vacuolar morphologies from different eukaryotic lineages: the discoban Naegleria gruberi and the amoebozoan slime mold Dictyostelium discoideum. Using quantitative cell biology, we find that although these species respond differently to osmotic challenges, they both use vacuolar-type proton pumps for filling contractile vacuoles and actin for osmoregulation, but not to power water expulsion. We also use analytical modeling to show that cytoplasmic pressure is sufficient to drive water out of contractile vacuoles in these species, similar to findings from the alveolate Paramecium multimicronucleatum. These analyses show that cytoplasmic pressure is sufficient to drive contractile vacuole emptying for a wide range of cellular pressures and vacuolar geometries. Because vacuolar-type proton-pump-dependent contractile vacuole filling and pressure-dependent emptying have now been validated in three eukaryotic lineages that diverged well over a billion years ago, we propose that this represents an ancient eukaryotic mechanism of osmoregulation.
Topics: Cytosol; Dictyostelium; Osmolar Concentration; Water-Electrolyte Balance; Vacuoles; Eukaryota; Water
PubMed: 37478864
DOI: 10.1016/j.cub.2023.06.061