Biology subjects

T S, K. P.

Publications and source records attributed to T S, K. P..

4 recordsLinked to original sources

bioRxiv2026

Temporal phosphoproteomics reveals rapid restoration of kinase signaling by Glycyrrhiza glabra in a rotenone-induced Parkinson disease model

Parkinsons disease is a progressive neurodegenerative disorder associated with mitochondrial dysfunction, oxidative stress, impaired autophagy, and dysregulated cellular signaling pathways. Although Glycyrrhiza glabra has been reported to exhibit neuroprotective properties, the early phosphorylation-mediated signaling mechanisms underlying its protective effects remain poorly understood. In this study, we employed a Tandem Mass Tag (TMT)-based temporal quantitative phosphoproteomic approach to investigate early signaling events associated with Glycyrrhiza glabra-mediated neuroprotection in a rotenone-induced in vitro PD model. Differentiated IMR-32 neuronal cells were treated with rotenone alone or in combination with Glycyrrhiza glabra extract, and phosphoproteomic alterations were analyzed at 2, 5, 15, and 30 minutes using liquid chromatography coupled with tandem mass spectrometer. Temporal phosphoproteomic analysis identified 6,424 phosphopeptides corresponding to 2,368 phosphoproteins and 5,468 phosphorylation sites. Comparative analysis revealed extensive phosphorylation rewiring induced by rotenone and restoration of several dysregulated phosphorylation events following Glycyrrhiza glabra co-treatment. More than 130 phosphoproteins and multiple kinase-associated signaling pathways were dynamically regulated across the temporal conditions. Kinase enrichment analysis identified restoration of several critical kinases, including AKT1, MTOR, MAPK1/3, PRKACA, PRKCD, and GSK3A/B, which are associated with neuronal survival, stress adaptation, and autophagy. Integrated pathway and kinase-substrate interaction analyses further revealed enrichment of AMPK signaling, FOXO signaling, receptor tyrosine kinase signaling, RNA processing, and cell-cycle regulatory pathways. Notably, several spliceosome-associated phosphoproteins demonstrated dynamic phosphorylation changes during the early neuroprotective response. Collectively, this study provides a detailed temporal phosphoproteomic landscape of early signaling events associated with Glycyrrhiza glabra-mediated neuroprotection and highlights kinase-driven signaling pathways that may represent potential therapeutic targets in Parkinsons disease.

neuroscience↗

bioRxiv2024

PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum

Malaria parasite transits through distinct developmental stages during its life cycle in the human and mosquito host, which includes unique asynchronous division in the erythrocytes. The switch from its asexual stage to sexual forms, which is critical for disease transmission, is intricately regulated but signalling pathways involved in this process have remained unknown. In the present study, we report a novel signalling pathway involving Protein Phosphatase PfPPM2, which regulates asexual division of the parasite as well as its conversion to sexual forms. Phosphoproteomics revealed that PfPPM2 may regulate the phosphorylation of key proteins involved in chromatin remodelling and protein translation. One of the key PfPPM2-targets that emerged from these studies was Heterochromatin Protein 1 (HP1), a regulator of heritable gene silencing which contributes to both mitotic proliferation as well as sexual commitment of the parasite. We demonstrate that PfPPM2 promotes sexual conversion by regulating the interaction between HP1, H3K9me3 and chromatin and it achieves this by dephosphorylating S33 of HP1. Regulation of HP1 and Histone H3 by PfPPM2 may also contribute to division. In addition, PfPPM2 also regulates protein synthesis in the parasite by repressing the phosphorylation of initiation factor eIF2, which is likely to contribute to parasite division and possibly sexual differentiation.

microbiology↗

bioRxiv2023

Identification of merozoite secreted repertoire and immuno-pharmacological inhibition of a novel host-parasite interaction to block malarial infection

BackgroundDuring the intra-erythrocytic proliferation of Plasmodium falciparum, the host erythrocyte invasion is regarded as a complex and tightly regulated process comprising multiple receptor-ligand interactions, and numerous secretory molecules. Proteins secreted sequentially from apical organelles of merozoites serve as adhesins that play a crucial role in RBC invasion and can serve as vaccine and therapeutic targets. MethodsPurified merozoites were triggered to discharge apical organelle contents by exposure to ionic conditions mimicking that of blood plasma. The secreted proteins were subjected to tandem mass spectrometry, and a well-characterized invasion ligand, RhopH3, was identified. A novel RhopH3 receptor, 14-3-3{square} was unearthed using a Bacterial two-hybrid approach. This interaction was confirmed using multiple biophysical and biochemical approaches. We were successful in disrupting this interaction using a de novo peptide binder of 14-3-3{square}, and we subsequently assessed its effect on merozoite invasion. ResultsA total of 66 proteins were identified in the secretory fraction with apical organellar or merozoite membrane localization. The well-known adhesin, RhopH3 was also identified and its interaction with the host phosphopeptide-binding protein, 14-3-3{square} was established. We also discovered a de novo peptide with the potency to disrupt this crucial interaction, thereby blocking merozoite invasion. ConclusionWe, for the first time, report the secretory repertoire of plasmodium merozoite. Our study shows the importance of the erythrocyte protein, 14-3-3{square} during the invasion process and paves the way for developing anti-malarial peptides or small molecules that inhibit the host-pathogen interaction, hence abrogating the invasion process.

microbiology↗

bioRxiv2022

Exome sequencing identifies variants associated with semen quality in Holstein Friesian and Hallikar bulls.

Effective fertility of bulls is dependent on semen quality, often determined based on standard semen evaluation tests. Here we report Whole Exome Sequencing (WES) of 12 bulls from two breeds Holstien Friesian and Hallikar selected based on Ejaculate Rejection Rate (ERR). We explored the possibility of identifying genetic variants from the conserved protein coding regions of genome. A total of 10,510 SNPs and 10.236 INDELs were identified post alignment against reference genome (ARS-UCD 1.2) and were annotated using SnpEff. The number of variants with high and modifier functional impact detected were 145 and 19,122, respectively. Genetic variants common to both high and low ERR group bulls among Holstein Friesian were 08 and in Hallikarthe common variants were 51. Prominent genesviz. UCP2, PANK2, GPD2, PTPRG, LARP7, EZH1, DENND1B and TDRD9 with a role in determining the semen quality were observed to be carriers of the genetic variant.

genomics↗