Biology subjects

Durso, W.

Publications and source records attributed to Durso, W..

4 recordsLinked to original sources

bioRxiv2025

NanTex enables computational multiplexing and phenotyping of organelles across super-resolution modalities

Super-resolution microscopy (SRM) enables nanoscale visualization of cellular organelles but remains constrained by spectral overlap, labeling requirements, and temporal offsets in multicolor imaging. We present NanTex, a deep learning framework that introduces nanotexture as a universal descriptor of subcellular organization and achieves probabilistic demixing of multiple organelles from single-channel SRM images. Unlike segmentation methods that enforce exclusivity, NanTex preserves overlapping morphologies, enabling faithful reconstruction even in crowded regions. Trained on small curated datasets with augmentation, NanTex generalized across SMLM, MINFLUX, STED, SIM, and live-cell Airyscan, with modality-specific retraining where necessary. Demonstrated on cytoskeletal, endomembrane, and metabolic organelles, NanTex achieved high-fidelity reconstructions and extended uniquely to live-cell imaging, where it eliminated temporal misalignment and enabled quantitative tracking of vesicle-like ER subdomains. Notably, NanTex enables quantitative dynamic readouts directly from single-channel live-cell data, revealing and tracking hidden subdomains in real time without the need for additional labels. Beyond multiplexing, NanTex supported computational phenotyping by distinguishing structurally distinct yet molecularly identical populations, exemplified by nocodazole-induced microtubule depolymerization and its glyoxal-mediated modulation. Together, these results establish nanotexture as a paradigm-shifting descriptor for organelle identity and position NanTex as a modality-agnostic, label-efficient, and live-cell-ready strategy for quantitative nanoscale biology. Significance StatementNanTex reframes multiplexing as texture-based demixing, introducing nanotexture as a universal fingerprint of organelle identity. By enabling quantitative, label-efficient reconstructions across SRM modalities and live-cell phenotyping, including vesicle tracking from single-channel data, NanTex opens a path to studying organelle remodeling and disease progression with unprecedented fidelity across SRM modalities.

biophysics↗

bioRxiv2025

The microcephaly-associated protein YIPF5 differentially regulates ER-export

YIPF5 is a small ER-membrane protein implicated in ER-Golgi transport. Mutations in YIPF5 cause MEDS2 (microcephaly with simplified gyral pattern, epilepsy, and neonatal diabetes syndrome), a fatal disorder manifesting in early childhood. We demonstrate that YIPF5 is involved in ER export of a subset of proteins, including cargoes of the ER-export receptor SURF4, with which it directly interacts. In YIPF5 knockout cells, we observe a shift in the cell surface and secretome composition, marked by reduced neuronal adhesion molecules and increased secretion of ER chaperones influencing cell migration. YIPF5 depletion enhances cell migration in a wound-healing assay and alters SURF4 localization, causing elongated ERGIC53- and Rab1-positive tubules from COPII-labeled ER exit sites. Kinetic analysis suggests that YIPF5 negatively regulates SURF4-mediated ER export. In utero knockdown of Yipf5 in embryonic mouse brains induces premature neuronal migration and abnormal neuronal morphology. These findings suggest that YIPF5 and SURF4 coordinate ER export, and disruption may underlie cortical development defects leading to microcephaly.

cell biology↗

bioRxiv2024

The Aging Synapse: An Integrated Proteomic And Transcriptomic Analysis

An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between transcriptome and proteome at soma and synaptic level during aging. Proteomic and transcriptomic data analysis reveal that, in young animals, proteins and transcripts are correlated and synaptic regulation is driven by changes in the soma. During aging, there is a decoupling between transcripts and proteins and between somatic and synaptic compartments. Furthermore, soma-synapse gradient of ribosomal genes changes upon aging, i.e. ribosomal transcripts are less abundant and ribosomal proteins are more abundant in synaptic compartment of old mice with respect to younglings. Additionally, transcriptomics data highlight a difference in the splicing of certain synaptic mRNA with aging. Taken together, our data provide a valuable resource for the study of the aging synapse.

neuroscience↗

bioRxiv2023

A YIPF5-GOT1A/B complex directs a transcription independent function of ATF6 in ER export

Exit from the endoplasmic reticulum is mediated by the Sar1/COPII machinery and a number of accessory factors. How the initial steps of cargo recruitment upstream of Sar1/COPII are mediated remains unclear, but the dihydropyridine FLI-06 inhibits cargo recruitment into ER exit sites. Here, we used chemical genetics screening approaches in conjunction with FLI-06 treatment and identified the ER membrane proteins YIPF5 and GOT1A/B as putative components of early export processes. Surprisingly, the two homologous proteins GOT1A and GOT1B, coded by GOLT1A and GOLT1B, respectively, exhibited opposite functions after treatment with FLI-06: increasing the expression of GOT1A or reducing the expression of GOT1B or YIPF5 prevented inhibition of ER-export by FLI-06. Inhibiting ER export with FLI-06 elicited a specific ER stress-related gene expression signature distinct from the ER-stress signature induced by Thapsigargin. The interactomes of GOT1A and GOT1B suggested a connection to ER-stress mediators. Moreover, RNA-Seq data showed that FLI-06-induced genes are strongly enriched for ATF6 target genes which are suppressed by GOLT1A overexpression or GOLT1B knock-down. This suggests that ATF6 signaling is involved in FLI-06-mediated toxicity, and we could demonstrate that siRNA-mediated knock-down or specific inhibitor of ATF6 rescued cells from FLI-06-mediated cell death. Knock-down or inhibition of ATF6 is sufficient to resume transport from the ER under FLI-06-treatment, suggesting that ATF6 is directly involved in the FLI-06-mediated ER-export block. Surprisingly, our data show that this ATF6 function is independent of de novo transcription, implying a novel, transcription-independent function of ATF6.

cell biology↗