Biology subjects

Hung, C.-Y.

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

4 recordsLinked to original sources

bioRxiv2023

Growth-dependent concentration gradient of the oscillating Min system in Escherichia coli

The Min system contributes to the spatiotemporal regulation of division sites in Escherichia coli. The MinD and MinE proteins of this system self-organize into oscillatory waves in the form of concentration gradients. How the intracellular Min protein concentration gradients are coordinated with cell growth to achieve spatiotemporal accuracy of cell division is unknown. Here, we report that the MinD concentration gradient becomes progressively steeper as cells elongate, suggesting that the division inhibitory activity at the midcell also decreases with cell growth. Interestingly, the oscillation period appears relatively stable across different cell lengths. Similar features were found in cells under carbon stress conditions, but the gradient was even steeper, likely favoring division at shorter cell lengths. The length-dependent variation of the concentration gradient was further examined in silico using a reaction-diffusion model, which not only supported the above features, but also revealed a decrease in the midcell concentration as the shape of the gradient becomes steeper in growing cells. This growth-dependent regulation of the midcell concentration of MinD may be coupled with the FtsZ ring formation through the MinD-interacting protein MinC. We found that the variable concentration gradients occur by coordinating the reaction rates of the recruitment of MinD and MinE to the membrane and the recharging of MinD with ATP in the cytoplasm. In conclusion, this work uncovers the plasticity of MinD concentration gradients during interpolar oscillations throughout cell growth, an intrinsic property integrated during cell division.

cell biology↗

bioRxiv2022

A rapid alkalinization factor-like peptide EaF82 impairs tapetum degeneration during pollen development

In plants, timely degeneration of tapetal cells is essential for providing nutrients and other substances to support pollen development. Rapid alkalinization factors (RALFs) are small, cysteine-rich peptides known to be involved in various aspects of plant development and growth, and defense against biotic and abiotic stresses. However, the functions of most of them remain unknown, while no RALF has been reported to involve in tapetum degeneration. In this study, we demonstrated that a novel cysteine-rich peptide EaF82 isolated from shy-flowering Golden Pothos plants is a RALF-like peptide and displays alkalinizing activity. Its heterologous expression in Arabidopsis delayed tapetum degeneration and reduced pollen production and seed yields. RNAseq, RT-qPCR and biochemical analyses showed that overexpressing EaF82 down-regulated a group of genes involved in pH changes, cell wall modifications, tapetum degeneration and pollen maturation as well as seven endogenous Arabidopsis RALF genes, and decreased proteasome activity and ATP levels. Yeast two-hybrid screening identified AKIN10, a subunit of energy-sensing SnRK1 kinase, to be its interacting partner. Our study reveals a possible regulatory role for RALF peptide in tapetum degeneration and suggests that EaF82 action may be mediated through AKIN10 leading to the alteration of transcriptome and energy metabolism, thereby causing ATP deficiency and impairing pollen development.

plant biology↗

bioRxiv2022

Mutant huntingtin exon-1 impaired GTPCH and DHFR expression in plants and mice

Pathophysiology associated with Huntingtons disease (HD) has been studied extensively in various cell and animal models since the 1993 discovery of the mutant huntingtin (mHtt) with abnormally expanded polyglutamine (polyQ) tracts as the causative factor. However, the sequence of early pathophysiological events leading to HD still remains elusive. To gain new insights into the polyQ-induced early pathogenic events, we expressed Htt exon1 (Httex1) with a normal (21), or an extended (42 or 63) number of polyQ in tobacco plants, which lack an Htt ortholog to avoid any associated effects from endogenous Htt. Here, we show that transgenic plants accumulated Httex1 proteins with corresponding polyQ tracts, and that mHttex1 induced protein aggregation and affected plant growth, especially root and root hair development, in a polyQ length-dependent manner. Quantitative proteomic analysis of young roots from severely affected Httex1Q63 and unaffected Httex1Q21 plants showed that the most impaired protein by polyQ63 is a GTP cyclohydrolase I (GTPCH) along with many its related one-carbon (C1) metabolic pathway enzymes. GTPCH is a key enzyme involved in folate biosynthesis in plants and tetrahydrobiopterin (BH4) biosynthesis in mammals. Validating studies in 4-week-old R6/2 HD mice expressing a mHttex1 showed reduced levels of GTPCH and dihydrofolate reductase (DHFR, a key folate utilization/alternate BH4 biosynthesis enzyme), and impaired C1 and BH4 metabolisms. Our findings from mHttex1 plants and mice reveal impaired expressions of GTPCH and DHFR and contribute to a better understanding of mHtt-altered C1 metabolism and C1 interconnected BH4 metabolism leading to the pathogenesis of HD.

molecular biology↗

bioRxiv2021

A Recombinant Multivalent Vaccine (rCpa1) Induces Protection for C57BL/6 and HLA Transgenic Mice Against Pulmonary Infection with Both Species of Coccidioides

Coccidioidomycosis is caused by Coccidioides posadasii (Cp) and Coccidioides immitis (Ci) that have 4-5% differences in their genomic sequences. There is an urgent need to develop a human vaccine against both species. A previously created recombinant antigen (rCpa1) that contains multiple peptides derived from Cp isolate C735 is protective against the autologous isolate. The focus of this study is to evaluate cross-protective efficacy and immune correlates by the rCpa1- based vaccine against both species of Coccidioides. DNA sequence analyses of the homologous genes for the rCpa1 antigen were conducted for 39 and 17 clinical isolates of Cp and Ci, respectively. Protective efficacy and vaccine-induced immunity were evaluated for both C57BL/6 and human HLA-DR4 transgenic mice against 5 highly virulent isolates of Cp and Ci. There are a total of 7 amino acid substitutions in the rCpa1 antigen between Cp and Ci. Both C57BL/6 and HLA-DR4 mice that were vaccinated with a rCpa1 vaccine resulted in significant reduction of fungal burden and increased numbers of IFN-{gamma}- and IL-17-producing CD4+ T cells in the first 2 weeks post-challenge. These data support that rCpa1 has cross-protection activity against Cp and Ci pulmonary infection through activation of early Th1 and Th17 responses.

immunology↗