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Yu, Y.-C.

Publications and source records attributed to Yu, Y.-C..

6 recordsLinked to original sources

SWEET family transporters act as water conducting carrier proteins in plants

AbstractDedicated water channels are involved in the facilitated diffusion of water molecules across the cell membrane in plants. Transporter proteins are also known to transport water molecules along with substrates, however the molecular mechanism of water permeation is not well understood in plant transporters. Here, we show plant sugar transporters from the SWEET (Sugar Will Eventually be Exported Transporter) family act as water-conducting carrier proteins via a variety of passive and active mechanisms that allow diffusion of water molecules from one side of the membrane to the other. This study provides a molecular perspective on how plant membrane transporters act as water carrier proteins, a topic that has not been extensively explored in literature. Water permeation in membrane transporters could occur via four distinct mechanisms which form our hypothesis for water transport in SWEETs. These hypothesis are tested using molecular dynamics simulations of the outward-facing, occluded, and inward-facing state of AtSWEET1 to identify the water permeation pathways and the flux associated with them. The hydrophobic gates at the center of the transport tunnel act as a barrier that restricts water permeation. We have performed in silico single and double mutations of the hydrophobic gate residues to examine the changes in the water conductivity. Surprisingly, the double mutant allows the water permeation to the intracellular half of the membrane and forms a continuous water channel. These computational results are validated by experimentally examining the transport of hydrogen peroxide molecules by the AtSWEET family of transporters. We have also shown that the transport of hydrogen peroxide follows the similar mechanism as water transport in AtSWEET1. Finally, we conclude that similar water-conduction states are also present in other SWEET transporters due to the high sequence and structure conservation exhibited by this transporter family.

biophysics↗

MvPPT: a highly efficient and sensitive pathogenicity prediction tool for missense variants

Next generation sequencing technologies both boost the discovery of variants in the human genome and exacerbate the challenges of pathogenic variant identification. In this study, we developed mvPPT (Pathogenicity Prediction Tool for missense variants), a highly sensitive and accurate missense variant classifier based on gradient boosting. MvPPT adopts high-confidence training sets with a wide spectrum of variant profiles, and extracts three categories of features, including scores from existing prediction tools, allele, amino acid and genotype frequencies, and genomic context. Compared with established predictors, mvPPT achieved superior performance in all test sets, regardless of data source. In addition, our study also provides guidance for training set and feature selection strategies, as well as reveals highly relevant features, which may further provide biological insights of variant pathogenicity.

bioinformatics↗

The hexose transporter SWEET5 confers galactose sensitivity to Arabidopsis pollen via the galactokinase GALK

Galactose is an abundant and essential sugar used for the biosynthesis of many macromolecules in different organisms, including plants. Galactose metabolism is tightly and finely controlled since excess galactose and derivatives are inhibitory. In Arabidopsis, root growth and pollen germination were strongly inhibited by excess galactose. However, the mechanism of galactose induced inhibition during pollen germination remains obscure. In this study, we characterized a plasma-membrane localized transporter, AtSWEET5, that transports glucose and galactose. SWEET5 protein level started to accumulate at the tricellular stage of pollen development and peaked in mature pollen before rapidly declining after pollen was germinated. SWEET5 levels are responsible for the dosage-dependent sensitivity of galactose and galactokinase (GALK) is essential for the inhibitory effects of galactose during pollen germination. Overall, SWEET5 and GALK contribute to the maintenance of galactose metabolic homeostasis during pollen germination. SWEET5 serves as a major low-affinity hexose transporter at the early stage of pollen germination. One-sentence summarySWEET5 mediates pollen galactose sensitivity via GALK that is required for efficient galactose uptake in pollen during pollen germination.

plant biology↗

Locally restricted glucose availability in the embryonic hypocotyl determines seed germination under ABA treatment

O_LIAbiotic stresses directly affect seed germination, plant growth, and reproduction. Seed germination is a complex and energy-demanding process, involving diverse physical, metabolic and cellular events, and is controlled by intrinsic and environmental cues. Abiotic stresses involving abscisic acid (ABA) inhibit seed germination by suppressing physiological processes essential for completion of germination. It remains unclear whether the component tissues of an embryo respond to stress, and are suppressed differentially. C_LIO_LIHere we used a genetically engineered FRET sensor to show that ABA significantly affected the spatiotemporal distribution of glucose (Glc) in lower hypocotyl region. Transcriptome analysis and 14C-Glc uptake assay suggested that Glc limitation in the embryonic hypocotyl was largely due to suppressed sugar partitioning along with enhanced sugar metabolism. The loss-of-function mutants of ABA-induced sucrose-phosphate synthase (SPS) genes accumulated more Glc, leading to ABA insensitivity during germination. In addition, we identified molecular signatures that Glc antagonizes ABA by globally counteracting the ABA influence on gene expression, including expansin (EXP) family genes that are inhibited by ABA. C_LIO_LIThis study presents a new perspective on the interaction between ABA and Glc in response to external stimuli, which restricts Glc availability and thereby controls the transition from seed to seedling. C_LI

plant biology↗

Early-generated interneurons regulate neuronal circuit formation during early postnatal development

A small subset of interneurons that are generated earliest as pioneer neurons are the first cohort of neurons that enter the neocortex. However, it remains largely unclear whether these early-generated interneurons (EGIns) predominantly regulate neocortical circuit formation. Using inducible genetic fate mapping to selectively labeled EGIns and pseudo-random interneurons (pRIns), we found that EGIns exhibited more mature electrophysiological and morphological properties and higher synaptic connectivity than pRIns at early postnatal stages. In addition, when stimulating one cell, the proportion of EGIns that influence spontaneous network synchronization is significantly higher than that of pRIns. Importantly, toxin-mediated ablation of EGIns after birth significantly reduce spontaneous network synchronization and decrease inhibitory synaptic transmission during the first postnatal week. These results suggest that EGIns can shape developing networks and may contribute to the refinement of neuronal connectivity before the establishment of the adult neuronal circuit.

neuroscience↗

Eye opening differentially modulates inhibitory synaptic transmission in the developing visual cortex

Eye opening, a natural and timed event during animal development, influences cortical circuit assembly and maturation; yet, little is known about its precise effect on inhibitory synaptic connections. Here we show that coinciding with eye opening, the strength of unitary inhibitory postsynaptic currents (uIPSCs) from somatostatin-expressing interneurons (SST-INs) to nearby excitatory neurons, but not interneurons, sharply decreases in layer 2/3 of the mouse visual cortex. In contrast, the strength of uIPSCs from fast-spiking interneurons (FS-INs) to excitatory neurons significantly increases during eye opening. More importantly, these developmental changes can be prevented by dark rearing or binocular lid suture, and reproduced by artificial opening of sutured lids. Mechanistically, this differential maturation of synaptic transmission is accompanied by a significant change in the postsynaptic quantal size. Together, our study reveals a differential regulation in GABAergic circuits in the cortex driven by eye opening likely crucial for cortical maturation and function.

neuroscience↗