-
rabindra.tharu.np@gmail.com
·
Caspase-2 is a condensate-mediated deubiquitinase in protein quality control
Protein ubiquitination plays a critical role in protein quality control in response to cellular stress. The excessive accumulation of ubiquitinated conjugates can be detrimental to cells and is recognized as a hallmark of multiple neurodegenerative diseases. However, an in-depth understanding of how the excessive ubiquitin chains are removed to maintain ubiquitin homeostasis post stress remains…
-
rabindra.tharu.np@gmail.com
·
ARF1 compartments direct cargo flow via maturation into recycling endosomes
Cellular membrane homoeostasis is maintained via a tightly regulated membrane and cargo flow between organelles of the endocytic and secretory pathways. Adaptor protein complexes (APs), which are recruited to membranes by the small GTPase ARF1, facilitate cargo selection and incorporation into trafficking intermediates. According to the classical model, small vesicles would facilitate bi-directional long-range transport…
-
rabindra.tharu.np@gmail.com
·
Recording morphogen signals reveals mechanisms underlying gastruloid symmetry breaking
Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates.…
-
rabindra.tharu.np@gmail.com
·
An architectural role of specific RNA-RNA interactions in oskar granules
Ribonucleoprotein (RNP) granules are membraneless condensates that organize the intracellular space by compartmentalization of specific RNAs and proteins. Studies have shown that RNA tunes the phase behaviour of RNA-binding proteins, but the role of intermolecular RNA-RNA interactions in RNP granules in vivo remains less explored. Here we determine the role of a sequence-specific RNA-RNA kissing-loop…
-
rabindra.tharu.np@gmail.com
·
Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition
Brain metastases (BrMs) evade the immune response to develop in the brain, yet the mechanisms of BrM immune evasion remains unclear. This study shows that brain astrocytes induce the overexpression of neuronal-specific cyclin-dependent kinase 5 (Cdk5) in breast cancer-derived BrMs, which facilitates BrM outgrowth in mice. Cdk5-overexpressing BrMs exhibit reduced expression and function of the…
-
rabindra.tharu.np@gmail.com
·
A size filter at the Golgi regulates apical membrane protein sorting
Despite decades of research, apical sorting of epithelial membrane proteins remains incompletely understood. We noted that apical cytoplasmic domains are smaller than those of basolateral proteins; however, the reason for this discrepancy is unknown. Here we used a synthetic biology approach to investigate whether a size barrier at the Golgi apparatus might hinder apical sorting…
-
rabindra.tharu.np@gmail.com
·
LIANA+ provides an all-in-one framework for cell-cell communication inference
The growing availability of single-cell and spatially resolved transcriptomics has led to the development of many approaches to infer cell-cell communication, each capturing only a partial view of the complex landscape of intercellular signalling. Here we present LIANA+, a scalable framework built around a rich knowledge base to decode coordinated inter- and intracellular signalling events…
-
rabindra.tharu.np@gmail.com
·
A phosphorylation-controlled switch confers cell cycle-dependent protein relocalization
Tools for acute manipulation of protein localization enable elucidation of spatiotemporally defined functions, but their reliance on exogenous triggers can interfere with cell physiology. This limitation is particularly apparent for studying mitosis, whose highly choreographed events are sensitive to perturbations. Here we exploit the serendipitous discovery of a phosphorylation-controlled, cell cycle-dependent localization change of the…
-
rabindra.tharu.np@gmail.com
·
Retinoic acid induces human gastruloids with posterior embryo-like structures
Gastruloids are a powerful in vitro model of early human development. However, although elongated and composed of all three germ layers, human gastruloids do not morphologically resemble post-implantation human embryos. Here we show that an early pulse of retinoic acid (RA), together with later Matrigel, robustly induces human gastruloids with posterior embryo-like morphological structures, including…
-
rabindra.tharu.np@gmail.com
·
p16-dependent increase of PD-L1 stability regulates immunosurveillance of senescent cells
The accumulation of senescent cells promotes ageing and age-related diseases, but molecular mechanisms that senescent cells use to evade immune clearance and accumulate in tissues remain to be elucidated. Here we report that p16-positive senescent cells upregulate the immune checkpoint protein programmed death-ligand 1 (PD-L1) to accumulate in ageing and chronic inflammation. We show that…
