Biology subjects

Zhu, J.-H.

Publications and source records attributed to Zhu, J.-H..

3 recordsLinked to original sources

bioRxiv2023

SELENOT regulates endoplasmic reticulum calcium flux via SERCA2 and maintains dopaminergic DAT to protect against attention deficit hyperactivity disorder in mice

Attention deficit and hyperactivity disorder (ADHD) is a prevalent developmental disorder. SELENOT is an endoplasmic reticulum-resident selenocysteine-containing protein. We aimed to investigate the role of SELENOT in dopaminergic neurons. Results from Selenotfl/fl;Dat-cre mice showed that SELENOT deficiency in dopaminergic neurons resulted in ADHD-like behaviors including hyperlocomotion, recognition memory deficit, repetitive movement, and impulsivity. Dopamine metabolism, extrasynaptic dopamine, spontaneous excitatory postsynaptic currents in the striatum and electroencephalogram theta power were enhanced in Selenotfl/fl;Dat-cre mice, whereas dopaminergic neurons in the substantia nigra were slightly reduced but exhibited normal neuronal firing and little cellular stress. Among dopamine- associated proteins, dopamine transporter (DAT) level was remarkably reduced and monoamine oxidase A increased mildly in the striatum and/or midbrain of Selenotfl/fl;Dat-cre mice. The ADHD-like phenotype and DAT ablation were corroborated in Selenotfl/fl;Nestin- cre mice, but not in Selenotfl/fl;Gfap-cre mice. In vitro overexpression and knockdown analyses and RNA-sequencing data revealed that SELENOT causatively regulated DAT mRNA and protein expression through Ca2+ signaling and NURR1. SELENOT maintained cellular Ca2+ levels via interaction with endoplasmic reticulum SERCA2, but not IP3Rs and RYRs, as demonstrated by Ca2+ imaging, co-immunoprecipitation coupled with mass spectrometry, and colocalization analyses. Treatment with psychostimulants, amphetamine or methylphenidate, rescued the hyperactivity in Selenotfl/fl;Dat-cre mice. In conclusion, SELENOT in dopaminergic neurons is indispensable to maintain proper dopamine signaling in the midbrain against ADHD.

neuroscience↗

bioRxiv2020

Hypoxia-induced miR-92a regulates p53 signalling pathway and apoptosis by targeting calcium-sensing receptor in Genetically Improved Farmed Tilapia (Oreochromis niloticus)

miR-92a miRNAs are immune molecules that regulate apoptosis (programmed cell death) during the immune response. Apoptosis helps to maintain the dynamic balance in tissues of fish under hypoxia stress. The aim of this study was to explore the role and potential mechanisms of miR-92a in the liver of tilapia under hypoxia stress. We first confirmed that CaSR (encoding a calcium-sensing receptor) is a target gene of miR-92a in genetically improved farmed tilapia (GIFT) using luciferase reporter gene assays. In GIFT under hypoxia stress, miR-92a was up-regulated and CaSR was down-regulated in a time-dependent manner. Knocked-down CaSR expression led to inhibited expression of p53, TP53INP1 and caspase-3/8, reduced the proportion of apoptotic hepatocytes, and decreased the activity of calcium ions induced by hypoxia in hepatocytes. GIFT injected in the tail vein with an miR-92a agomir showed up-regulation of miR-92a and down-regulation of CaSR, p53, TP53INP1, and caspase-3/8 genes in the liver, resulting in lower serum alanine aminotransferase and aspartate aminotransferase activities under hypoxia stress. These findings suggest that stimulation of miR-92a interferes with hypoxia-induced apoptosis in hepatocytes of GIFT by targeting CaSR, thereby alleviating liver damage. These results provide new insights into the adaptation mechanisms of GIFT to hypoxia stress.

molecular biology↗

bioRxiv2019

Selective translation by alternative bacterial ribosomes

Alternative ribosome subunit proteins are prevalent in the genomes of diverse bacterial species but their functional significance is controversial. Attempts to study microbial ribosomal heterogeneity have mostly relied on comparing wild-type strains with mutants in which subunits have been deleted, but this approach does not allow direct comparison of alternate ribosome isoforms isolated from identical cellular contexts. Here, by simultaneously purifying canonical and alternative RpsR ribosomes from Mycobacterium smegmatis, we show that alternative ribosomes have distinct translational features compared with their canonical counterparts. Both alternative and canonical ribosomes actively take part in gene translation, although they translate a subset of genes with differential efficiency as measured by ribosome profiling. We also show that alternative ribosomes have a relative defect in initiation complex formation. Our work convincingly confirms the distinct and non-redundant contribution of alternative bacterial ribosomes for adaptation to hostile environments.\n\nSignificance StatementMany organisms, including most bacteria code for multiple paralogues of some ribosomal protein subunits. The relative contribution of these alternative subunits to ribosome function and gene translation is unknown and controversial. Furthermore, many studies on alternative ribosomes have been confounded by isolation of alternative and canonical ribosomes from different strains and/ or different growth conditions, potentially confounding results. Here, we show unequivocally that one form of alternative ribosome from Mycobacterium smegmatis actively engages in gene translation, but its translational profile from an identical cellular context is subtly different from canonical ribosomes. Given the prevalence of alternative ribosomal genes in diverse organisms, our study suggests that alternative ribosomes may represent a further layer of regulation of gene translation.

microbiology↗