Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2023.02.15.528619

Scribble, Lgl1, and myosin IIA interact with α/β-catenin to maintain epithelial junction integrity

Abedrabbo, M.·Sloomi, S.·Abu-leil, R.·Cohen-Kfir, E.·Ravid, S.
View original source ↗Export metadata ↓

Abstract

E-cadherin, - and {beta}-catenin (E-cadherin-catenin complex) together with the cytoskeleton build the core of Adherens junctions (AJs). Scribble and Lgl1 are tumor suppressors, and it has been reported that Scribble stabilizes the coupling of E-cadherin with catenins promoting epithelial cell adhesion, but the molecular mechanism remains unknown. Here, we investigated the role of Scribble, Lgl1, and myosin-IIA (NMII-A) in AJ integrity. We show that Scribble, Lgl1, and NMII-A reside in a complex with the E-cadherin-catenin complex. Depletion of either Scribble or Lgl1 disrupts the localization of E-cadherin-catenin complex to AJs. aPKC{zeta} phosphorylation of Lgl1 regulates AJ localization of Lgl1 and E-cadherin-catenin complex. Both Scribble and Lgl1 regulate the activation and recruitment of NMII-A at AJs. Finally, Scribble and Lgl1 are downregulated by TGF{beta}-induced EMT, and re-expression of Scribble or Lgl1 during EMT impedes its progression. Our results provide insight into the mechanism regulating AJ integrity by Scribble, Lgl1, and NMII-A.

Source connections

Explore related subjects

cell biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Abedrabbo, M., Sloomi, S., Abu-leil, R., Cohen-Kfir, E., Ravid, S.. 2023-02-15. Scribble, Lgl1, and myosin IIA interact with α/β-catenin to maintain epithelial junction integrity. https://doi.org/10.1101/2023.02.15.528619

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

High-content screening identifies FDA-approved activators of mitophagy

Mitochondrial diseases are highly heterogeneous disorders caused by defects in oxidative phosphorylation, for which only limited therapeutic options are available. The elimination of dysfunctional mitochondria via mitophagy activation is an attractive strategy to treat several mitochondrial diseases, irrespective of the underlying genetic defect. To identify pharmacological activators of this pathway, we performed a high-content screening of 1,971 FDA-approved compounds using cellular reporters of TFEB nuclear translocation and mitophagy. This screening identified 294 compounds that promoted TFEB translocation, nine of which increased the number of mitolysosomes without compromising cell viability or damaging mitochondria. Among the selected compounds, Meptazinol and Ponatinib emerged as the top-ranked mitophagy inducers in fibroblasts from patients with complex I and IV deficiency, respectively, and were prioritised for further characterisation. However, they did not rescue the bioenergetic defect, suggesting that the stimulation of mitophagy per se is not sufficient to ameliorate the OXPHOS defect in mitochondrial diseases. Overall, our findings establish a scalable platform for the identification of pharmacological activators of TFEB and identify candidate compounds for therapeutic modulation of mitophagy.

cell biology↗
bioRxiv2026

A LOV-domain photoreceptor mediates phototaxis in brown algae

Phototaxis enables motile cells to navigate light environments and plays a critical role in survival and reproduction across diverse eukaryotic lineages. This ability has evolved independently through distinct photoreceptor systems. Yet, the molecular mechanisms underlying phototaxis remain poorly understood in many major eukaryotic lineages, including stramenopiles. Here, combining functional genetics, cell biology and evolutionary analyses, we identify Helmchrome (HELM), a LOV-domain protein required for phototaxis in the brown alga Ectocarpus. HELM localizes to the posterior flagellum and is responsible for the characteristic flavin-associated fluorescence of brown algal gametes. Loss of HELM abolishes phototactic accumulation and directional orientation without affecting basal motility or fertilization, demonstrating its specific requirement for light-directed movement. Phylogenetic analyses reveal that HELM-like proteins are distributed across diverse stramenopile lineages and that their domain architecture evolved through repeated duplication of an ancestral RGS-LOV module. Our findings identify HELM as a key component of the light-sensing machinery in brown algae, provide a molecular explanation for the long-standing observation of flagellar flavin fluorescence, and reveal a distinct phototaxis system that expands the known diversity of eukaryotic light-sensing mechanisms.

cell biology↗
bioRxiv2026

A distinct chondrogenic progenitor population from human umbilical cord derived mesenchymal stromal cells for osteoarthritis therapy

Stem cell-based cartilage regeneration remains constrained by functional heterogeneity and phenotypic drift in conventional cell sources, compromising durable structural repair. Human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) represent an accessible, off-the-shelf cell source; however, their broad clinical utility is hampered by cellular heterogeneity, leaving the key chondrogenic subpopulation responsible for cartilage repair unresolved. By integrating single-cell transcriptomics with functional assays, we identified and prospectively isolated a distinct, highly expandable subpopulation of skeletal stem cell-like progenitors (U-CPCs) from the human umbilical cord, establishing an extra-skeletal cell source uniquely primed for joint restoration. Single-cell transcriptomics reveal their inherent regulatory landscape, uncovering a distinct transcriptional state uniquely primed for chondrogenesis. In comparison with conventional stem cells and other tissue-derived SSC-like populations (from umbilical cord, bone marrow, adipose tissue, and dental pulp), U-CPCs exhibit a markedly enhanced chondrogenic capacity. In both a mouse cartilage injury model and a rat osteoarthritis model, the administration of U-CPCs effectively mitigates joint degeneration and drives the restoration of a structurally sound, hyaline-like matrix. Mechanistically, U-CPCs secrete extracellular vesicles enriched with microRNA Let-7a-5p, which specifically modulates DUSP7/MAPK/ERK signaling in recipient chondrocytes, thereby restoring extracellular matrix homeostasis and promoting cartilage repair. By characterizing these specialized extra-skeletal progenitors and elucidating both their intrinsic chondrogenic priming and paracrine regulation of host tissue, this study establishes U-CPCs as a robust, lineage-restricted cellular source for osteoarthritis therapy.

cell biology↗