The serotonin transporter (SERT) terminates neurotransmission by transporting serotonin from the synapse into the pre-synaptic nerve terminal. Altered SERT function leads to several neurological diseases including depression, anxiety, mood disorders, and attention deficit hyperactivity disorders (ADHD). Accordingly SERT is the target for their pharmacological treatments, but also targeted by multiple drugs of abuse. Transport of serotonin by SERT is energized by the transmembrane electrochemical gradient of sodium. We used extensive molecular dynamics simulations to investigate the process of sodium binding to SERT, which is the first step in the transport cycle that leads to serotonin uptake. Comparing data from 51 independent simulations, we find a remarkably well-defined path for sodium entry and could identify two transient binding sites, while observing binding kinetics that are comparable to experimental data. Importantly, the structure and dynamics of the sodium binding sites indicate that sodium binding is accompanied by an induced-fit mechanism that leads to new conformations and reduces local dynamics.
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http://dx.doi.org/10.3389/fncel.2021.673782 | DOI Listing |
Plant Cell
January 2025
State Key Laboratory of Plant Environmental Resilience, China Agricultural University, Beijing 100193, China.
Salt stress causes ion toxicity in plant cells and limits plant growth and crop productivity. Sodium ions (Na+) are transported out of the cell and sequestered in the vacuole for detoxification under salt stress. The salt excretion system is controlled by the SALT OVERLY SENSITIVE (SOS) pathway, which consists of the calcium sensors SOS3 and SOS3-LIKE CALCIUM BINDING PROTEIN 8, the protein kinase SOS2, and the plasma membrane Na+/H+ antiporter SOS1.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China.
Purpose: Dry eye disease (DED) is a common ocular surface inflammatory disease with a complex pathogenesis. Herein, the role and effect of gasdermin E (GSDME) in DED pathogenesis were explored.
Methods: In vitro, flow cytometry, Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays were used to determine the effects of hyperosmotic stress on pyroptosis, apoptosis, and cell viability in human corneal epithelial cells (HCECs).
Biochem J
January 2025
University of Pittsburgh School of Medicine, Pittsburgh, United States.
The sodium phosphate cotransporter-2A (NPT2A) mediates basal and parathyroid hormone (PTH)- and fibroblast growth factor-23 (FGF23)-regulated phosphate transport in proximal tubule cells of the kidney. Both basal and hormone-sensitive transport require sodium hydrogen exchanger regulatory factor-1 (NHERF1), a scaffold protein with tandem PDZ domains, PDZ1 and PDZ2. NPT2A binds to PDZ1.
View Article and Find Full Text PDFNano Lett
January 2025
Key Laboratory of Advanced Structural Materials, Ministry of Education, and School of Materials Science and Engineering, Changchun University of Technology, Changchun 130012, China.
The growing market for sodium-ion batteries has stimulated interest in research on Prussian blue-type cathode materials. Iron hexacyanoferrate (FeHCF) is considered a desirable Prussian blue-type cathode, but the incomplete electrochemical property of its low-spin iron sites hinders its further practical application. In this paper, carboxymethyl cellulose is demonstrated to have an appropriate binding energy through DFT calculations, synthesize Prussian blue in situ, balance Fe and water in FeHCF, and introduce Fe vacancies to activate low-spin Fe sites.
View Article and Find Full Text PDFSmall
January 2025
Fujian Provincial Key Laboratory of Quantum Manipulation and New Energy Materials, College of Physics and Energy, Fujian Normal University, Fuzhou, Fujian, 350117, China.
Single-atom materials provide a platform to precisely regulate the electrochemical redox behavior of electrode materials with atomic level. Here, a multifield-regulated sintering route is reported to rapidly prepare single-atom zinc with a very high loading mass of 24.7 wt.
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