Biology subjects

Padhi, S.

Publications and source records attributed to Padhi, S..

4 recordsLinked to original sources

bioRxiv2026

Cell Mechanics Regulate Membrane Tubulation-Driven Trogocytosis in Adherent Cells

Trogocytosis is a widespread and physiologically important process in which one cell ingests fragments of another. It has been observed in diverse biological contexts, such as in Entamoeba histolytica, a human enteric parasite that nibbles host intestinal cells via trogocytosis, thereby invading the tissue and leading to lethal extra-intestinal disease, and in macrophages on interaction with adherent tumor monolayers. Despite its physiological relevance, knowledge of trogocytosis with adherent cells remains elusive. Here, we established a monolayer-based trogocytosis assay and uncovered a distinct membrane-tube-mediated trogocytic mechanism operative in adherent cells. We characterized it into four sequential events: contact, membrane tubulation, stretching, and scission. By targeting the proteic constituents of target cell stiffness, we show that trogocytic output exhibits a non-monotonic dependence on the viscoelastic properties of the target cell, with maximal uptake occurring in an intermediate mechanical regime. Further, we integrated live-cell trogocytosis observations with a viscoelastic model-based theoretical framework to propose a tube-breaking mechanism across distinct mechanical subtypes. Finally, using micropatterning, we demonstrated that target cell shape influences trogocytosis kinetics. This work suggests that trogocytosis is sensitive to the mechanical state of the target cell.

cell biology↗

bioRxiv2026

Microbiome contribution to Indy longevity in Drosophila

Reduction in the Indy (Im not dead yet) gene, a plasma membrane citrate transporter, in Drosophila and its homolog in worms extends lifespan by promoting metabolic homeostasis. Indy reduction delays the onset of aging-associated pathology in the fly midgut, including preservation of intestinal barrier integrity and intestinal stem cell homeostasis. Gut microbiota has broad impacts on host metabolism, health, and aging. Age-related dysbiosis impairs intestinal barrier function and drives mortality. However, the underlying mechanisms that link increased microbial load to frailty and negative effects on health remain mostly unclear. Here we show that Indy heterozygote flies have significantly lower bacterial load and increased diversity during aging compared to controls. However, the presence of the microbiome was not required for Indy lifespan extension, though removal of microbes did enhance the effects of Indy reduction on longevity, suggesting potential interactions between the microbiome and Indy. Indy down-regulation was linked to reduced expression of the JAK/STAT signaling ligands Upd3 and Upd2 in the midgut of young flies, which likely contributes to preserved intestinal stem cell homeostasis. Altogether, our results suggest that Indy reduction impacts microbiome load and composition, which preserves gut homeostasis and extends lifespan through impacts on JAK/STAT signaling pathway. Significance StatementIndy is a fly homologue of mammalian SLC13A5 (mSLC13A5) plasma membrane citrate transporter, a central metabolic regulator involved in health, longevity, and disease. Reduction of fly Indy gene activity preserves metabolic and intestinal stem cell homeostasis and extends longevity. Gut microbiota impacts host metabolism, health, and aging. Here we show that Indy reduction prevents age-associated increases in bacterial load and expression of the JAK/STAT signaling ligands Upd3, and Upd2, while maintaining microbiome diversity. These changes likely slow activation of epithelial cell turnover in the gut and contribute to downstream lifespan effects. As the role of INDY and microbiome are conserved across organisms, our study provides a framework to study underlying mechanisms of the effects of reduced Indy and the microbiome on health and longevity.

genetics↗

bioRxiv2020

The HIV-1 Vpu transmembrane domain topology and formation of a hydrophobic interface with BST-2 are critical for Vpu-mediated BST-2 downregulation

Viruses belonging to the M group of human immunodeficiency virus (HIV-1) are the most virulent among the four HIV-1 groups. One factor that distinguishes the M group HIV-1 from others is Vpu, a membrane localized accessory protein, which promotes the release of virions by neutralizing the antiviral host cell protein BST-2. To investigate if this activity is determined by the topology of Vpu or by conserved amino acid residues, we prepared chimeric forms of Vpu by replacing its transmembrane domain with those from its topological homologs. Although the chimeric Vpu proteins downregulated BST-2, these substantially reduced virus production as well. Molecular modeling studies on Vpu from different HIV-1 groups and the chimeric Vpu proteins showed that shape and the availability of a hydrophobic interface are more important for BST-2 antagonism than conservation of the amino acid sequence. Our data suggest that the HIV-1 Vpu-M protein has evolved topologically to interact with BST-2, and that the Vpu/BST-2 interface can be exploited as a target to limit HIV-1 replication.

cell biology↗

bioRxiv2018

Non-histone human chromatin protein, PC4 is critical for genomic integrity and negatively regulates autophagy

Multifunctional human transcriptional positive co-activator 4 (PC4) is a bonafide non-histone component of the chromatin and plays a pivotal role in the process of chromatin compaction and functional genome organization. Knockdown of PC4 expression leads to a drastic open conformation of the chromatin and thereby altered nuclear architecture, defects in chromosome segregation and changed epigenetic landscape. Interestingly, these defects do not induce cellular death but result in enhanced cellular proliferation possibly through enhanced autophagic activity. PC4 depletion confers significant resistance to gamma irradiation. Exposure to gamma irradiation further induced autophagy in these cells. Inhibition of autophagy by small molecule inhibitors as well as by silencing of a critical autophagy gene drastically reduces the survivability PC4 knockdown cells. On the contrary, complementation with wild type PC4 could reverse this phenomenon, confirming the process of autophagy as the key mechanism for radiation resistance in absence of PC4. These data connect the unexplored role of chromatin architecture in regulating autophagy during a stress condition such as radiation.

molecular biology↗