Biology subjects

Dongre, S.

Publications and source records attributed to Dongre, S..

5 recordsLinked to original sources

bioRxiv2025

Developing epidermis acquires nutrients from the external milieu by mTOR-dependent macropinocytosis

The vertebrate epidermis transitions from a simple bilayer to a complex, multilayered epithelium during development. Periderm, the outermost layer of the bilayered epidermis, is in direct contact with the external aquatic surrounding. While the barrier function of the epidermis is well established, the functional repertoire of the developing epidermis remains unclear. Using zebrafish, we uncover a function of the periderm in nutrient acquisition. Our findings reveal a developmentally regulated wave of macropinocytosis, which is further amplified by extracellular nutrients, leading to the formation of large endo-lysosomal compartments termed Stimulated Nutrient Activated Compartments (SNACs). We identify mTOR as a key integrator of developmental and nutrient-derived signals that modulate SNAC biogenesis. A global lipidomics analysis demonstrates that macropinocytosis-mediated uptake drives the production of metabolically relevant lipids and enhances animal survival when gut function is compromised. Our study identifies a hitherto unappreciated route of nutrient acquisition by the metabolically responsive developing epidermis. We propose that this mechanism fulfils a vital nutritional role, particularly during the transitional phase when maternally provided resources are depleting and the gut is not yet fully operational.

developmental biology↗

bioRxiv2024

Specificity in transcription factor clustering is encoded in the genome

Transcription factors (TFs) often form clusters in the nucleus. Clusters can facilitate transcription, but it remains unclear how they form. It has been suggested that clusters are seeded by the sequence-specific binding of TFs to DNA, and grow by IDR-IDR interactions that bring in more TFs. This model, however, does not explain how TFs can cluster in specific combinations. Here, we study TF clustering by quantitative imaging of Nanog, Pou5f3, and Sox19b in zebrafish embryos. Using mutant and chimaeric TFs, we show that the formation of a TF cluster requires the DBD as well as at least one of its IDRs. In contrast with the existing model, however, IDRs are not sufficient to join a pre-existing cluster. Instead, both IDR and DBD are needed. Thus, for any TF to join a cluster, motif recognition is required, which explains the specificity in cluster formation. Finally, we show that while IDRs are required to join a cluster, their amino acid sequence is interchangeable, and the DBD can confer specificity to any IDR. Taken together, our work changes the model of cluster formation and explains how specificity is achieved in the organization of transcriptional machinery in the nucleus.

cell biology↗

bioRxiv2024

Differential expression of GABARAPs in GBM renders temozolomide sensitivity in a p53-dependent manner

Glioblastoma (GBM) is one of the most debilitating and extremely aggressive tumors, with a median survival of less than a year. GBMs have high metastatic potential and frequently acquire chemoresistance. The current multimodal treatment approaches for GBM include surgical tumor resurrection, radiotherapy, and chemotherapy but these approaches leave the patient with long-term disabilities such as depletion of cognitive abilities, leukoencephalopathy, and recurrence in 6-8 months. Glioma cells are highly dependent on autophagy to survive and proliferate. Autophagy inhibition has proven to be a beneficial strategy for restricting glioma growth. However, the autophagy pathway cannot be efficiently targeted due to the lack of specific autophagy inhibitors. Understanding the vulnerabilities in autophagy gene expression can help to design better autophagy inhibitors. This study demonstrates the differential expression of GABARAP family members in low-grade glioma and GBM. Our study highlights the differential expression of GABARAP family members in response to autophagy inhibition and induction. Moreover, the knockdown of specific GABARAP family members enhanced proliferation and reduced temozolomide (TMZ) sensitivity of glial cells by decreasing the p53 expression. The selective expression pattern of GABARAP genes in Glioblastoma can be utilized to screen for patients who might respond better to temozolomide treatment. The differential expression of GABARAP family members highlights the subtle regulation of the autophagy pathway in response to environmental cues.

cancer biology↗

bioRxiv2018

Ca2+-activated K+ channels reduce network excitability, improving adaptability and energetics for transmitting and perceiving sensory information

Ca2+-activated K+ channels (BK and SK) are ubiquitous in synaptic circuits, but their role in network adaptation and sensory perception remains largely unknown. Using electrophysiological and behavioral assays and biophysical modelling, we discover how visual information transfer in mutants lacking the BK channel (dSlo-), SK channel (dSK-) or both (dSK-;;dSlo-) is shaped in the Drosophila R1-R6 photoreceptor-LMC circuits (R-LMC-R system) through synaptic feedforward-feedback interactions and reduced R1-R6 Shaker and Shab K+ conductances. This homeostatic compensation is specific for each mutant, leading to distinctive adaptive dynamics. We show how these dynamics inescapably increase the energy cost of information and distort the mutants motion perception, determining the true price and limits of homeostatic compensation in an in vivo genetic animal model. These results reveal why Ca2+-activated K+ channels reduce network excitability (energetics), improving neural adaptability for transmitting and perceiving sensory information.\n\nHighlightsO_LIHomeostatic plasticity in Drosophila dSlo-, dSK- and dSK-;;dSlo- null-mutants retains R1-R6 photoreceptors light information sampling while reducing other K+-conductances\nC_LIO_LIAs mutant R-LMC-R circuits rebalance synaptic loads homeostatically, R1-R6s become more depolarized, with dSK- and dSK-;;dSlo- responding faster and dSlo- slower, whilst LMC outputs oscillate, with dSK- responding faster and dSK-;;dSlo- and dSlo- slower than wild-type\nC_LIO_LIHomeostatic compensation in the mutant circuits impedes adaptation, increases the energy cost of visual information and distorts optomotor behavior\nC_LIO_LIHence, Ca2+-activated K+ channels improve adaptability and energetics for transmitting and perceiving sensory information\nC_LI

neuroscience↗

bioRxiv2016

Microsaccadic information sampling provides Drosophila hyperacute vision

Small fly eyes should not see fine image details. Because flies exhibit saccadic visual behaviors and their compound eyes have relatively few ommatidia (sampling points), their photoreceptors would be expected to generate blurry and coarse retinal images of the world. Here we demonstrate that Drosophila see the world far better than predicted from the classic theories. By using electrophysiological, optical and behavioral assays, we found that R1-R6 photoreceptors encoding capacity in time is maximized to fast high-contrast bursts, which resemble their light input during saccadic behaviors. Whilst over space, R1-R6s resolve moving objects at saccadic speeds beyond the predicted motion-blur-limit. Our results show how refractory phototransduction and rapid photomechanical photoreceptor contractions jointly sharpen retinal images of moving objects in space-time, enabling hyperacute vision, and explain how such microsaccadic information sampling exceeds the compound eyes optical limits. These discoveries elucidate how acuity depends upon photoreceptor function and eye movements.

neuroscience↗