Purpose: Hyperosmolar stress (HOS) is a major contributor to corneal epithelial cell damage in dry eye disease. We have previously shown that HOS damages mitochondria and impairs cell metabolism in corneal epithelial cells. Small extracellular vesicles (sEVs) are cell-derived lipid envelopes that are present in all body fluids, including tears. Prior studies suggest that sEV […]
FOXO3 regulated MIR503HG safeguards cellular quiescence by modulating PI3K/Akt pathway via miR-508/PTEN axis
Long noncoding RNAs (LncRNAs) have emerged as a class of important regulatory ncRNAs and are known to fine- tune numerous cellular processes including proliferation, differentiation and development; however, their role in quiescence still remains largely unexplored. A miRNA host gene lncRNA, MIR503HG, has been reported to play important role in cancer development. Here, we demonstrate […]
PRINCIPLES GOVERNING ENDOTHELIAL CAVEOLAE ORGANIZATION DURING ANGIOGENESIS
Caveolae, flask-shaped membrane invaginations highly enriched in endothelial cells, play a central role in buffering membrane tension, yet the principles governing their spatial organization remain elusive. This investigation sought to generate the most comprehensive and systematic analysis of blood vessel caveolar spatial organization. To do so, our group leveraged micropatterning technologies to impose precise biophysical […]
Neurodegeneration risk variants promote lysosomal TMEM106B fibrilaccumulation
Variants in TMEM106B and GRN, which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding […]
Effect of spatial heterogeneities on minimal stochastic models of cell polarity
Asymmetric self-organization is a hallmark of cell polarity, yet the diversity of observed polarization patterns is frequently attributed to specialized, complex biochemical mechanisms motifs beyond simple positive feedback. Here, we demonstrate that spatial heterogeneity alone fundamentally reshapes polarization dynamics within minimal stochastic reaction-diffusion processes. We show that weak differences in reaction rates between distinct spatial […]
Kinase-gated coincidence detection controls kinesin-driven lysosome transport
Kinesin motors drive long-range intracellular transport through coordinated cargo recognition and conformational autoregulation, yet the mechanisms that selectively control cargo engagement remain unclear. Here, we identify a phosphorylation-dependent gate on kinesin-1 activity mediated by the carboxy-terminal domain (CTD) of kinesin light chain 2 (KLC2). The KLC2 CTD is constitutively phosphorylated on multiple serine residues, suppressing […]
Vascular dilation modulates brain haematoma expansion in larval zebrafish
Intracerebral haemorrhage (ICH) is a severe form of stroke with high morbidity and mortality rates. For survivors, acute haematoma expansion strongly determines neurological outcome. Although blood pressure reduction is widely investigated as a strategy to limit haematoma growth, the haemodynamic mechanisms regulating haemorrhage development remain poorly understood. Zebrafish provide a tractable in vivo model to […]
Inhibition of V-ATPase function drives apoptosis via GCN1/GCN2 kinase signaling
Natural products are a rich source of bioactive molecules that have served both as templates for drug discovery and as tools to uncover fundamental biological processes. While characterizing the pro-apoptotic activity of the cyanobacterial metabolite Nostatin A, we identified vacuolar-type H+-ATPase (V-ATPase) as its molecular target and uncovered an unexpected signalling response preceding cell death […]
Dynamic UFMylation governs cellular fitness by coordinating multi-organelle proteostasis
Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like protein (UBL) covalently attached to substrates through a dedicated enzymatic cascade (UFMylation) and removed by specific proteases. Despite a key role in endoplasmic reticulum (ER)-ribosome homeostasis, the basis by which this UBL supports cell fitness remains elusive, as the essentiality of UFMylation machinery varies widely across hundreds of […]
Identification and functional investigation of Octopus vulgaris TRPV channels as potential nociceptors in cephalopods
Nociception is an essential response for organisms to avoid potential harm and promote survival. Its molecular determinants are largely conserved across Eumetazoa. TRPV receptors are polymodal ion channels exhibiting selective peripheral expression and functional coupling that underpins nociception and pain modulation in complex organisms. However, the execution of protective behaviours triggered by TRPVs is also […]
KDM2B controls HIF levels and activity through its JmjC and CxxC domains
Hypoxia-inducible factors (HIFs) are key regulators of cellular responses to low oxygen (hypoxia), controlling the expression of genes required for survival and adaptation. KDM2B, a chromatin-modifying enzyme, is a direct target of HIF-1, but its precise role in regulating HIF and the hypoxia response remains unclear. Here, we investigated the role of KDM2B in the […]
STING causes replication stress and nascent DNA degradation via SAMHD1
STING is a key innate immune adaptor, classically activated by cytosolic DNA via cGAS-cGAMP to induce type I interferon signaling. While its cytoplasmic role is well-defined, recent studies reveal that STING participates in non-canonical signaling pathways and localizes at the nuclear envelope and chromatin, where its functions remain poorly understood. In Hutchinson Gilford Progeria Syndrome […]