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Tsarouhas, V.

Publications and source records attributed to Tsarouhas, V..

3 recordsLinked to original sources

A Non-Transcriptional Mitotic Function of POU/Oct Factors Ensures Spindle Stability and Chromosome Segregation

POU/Oct transcription factors are critical regulators of cellular processes, including proliferation, cell fate determination, and cancer. Despite their importance, the specific molecular mechanisms by which they influence cell division remain largely unclear. Here, we show that Nub/Pdm1, a Drosophila homolog of human POU2F1/Oct1, is essential for accurate mitotic progression in a non-transcriptional manner. Live imaging and immunostaining in Drosophila embryos reveal that its depletion leads to disorganized spindles, aberrant chromosome segregation and delayed mitotic progression. Similarly, reduction of POU2F1/Oct1 in live human cells caused disorganized mitotic spindles and spindle collapse. Nub/Pdm1 is enriched within the mitotic spindles and this recruitment is independent of its sequence-specific DNA binding. Instead, it depends on the integrity of spindle microtubules and is regulated by mitosis-related motor proteins, and kinases. Our findings identify both fly Nub/Pdm1 and human Oct1 as important regulators of mitotic progression, acting to maintain spindle stability and proper elongation. The non-transcriptional mitotic role of Nub/Pdm1 reveals a previously unrecognized mechanism of POU/Oct proteins and provides new insight into their potential oncogenic properties. Highlights- Nub/Pdm1 is vital for accurate mitotic progression in a non-transcriptional manner - Nub/Pdm1 preserves spindle integrity during rapid syncytial nuclear divisions - Nub/Pdm1 spindle enrichment depends on mitotic factors and intact microtubules - Nub and human Oct1 ensure proper chromosome segregation

cell biology↗

Scavenger receptor endocytosis controls apical membrane morphogenesis in the Drosophila airways

The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In the Drosophila airway tree, the interplay of apical ECM components with the underlying membrane and cytoskeleton controls tube elongation, but the link between ECM composition with apical membrane morphogenesis and tube size regulation is elusive. Here, we characterized Emp (epithelial membrane protein), a Drosophila CD36-homologue belonging to the scavenger receptor class B protein-family. emp mutant embryos fail to internalize the luminal chitin deacetylases Serp and Verm at the final stages of airway maturation and die at hatching with liquid filled airways. Emp localizes in apical epithelial membranes and shows cargo selectivity for LDLr-domain containing proteins. emp mutants also display over elongated tracheal tubes with increased levels of the apical proteins Crb, DE-cad and phosphorylated Src (p-Src). We show that Emp associates and organizes the {beta}H-Spectrin cytoskeleton and is itself confined by apical F-actin bundles. Overexpression or loss of its cargo protein Serp lead to abnormal apical accumulations of Emp and perturbations in p-Src levels. We propose that during morphogenesis, Emp senses and responds to luminal cargo levels by initiating apical membrane endocytosis along the longitudinal tube axis and thereby restricts airway elongation.

developmental biology↗

Yorkie controls tube length and apical barrier integrity in the developing Drosophila airways

Epithelial organ size and shape depend on cell shape changes, cell-matrix communication and apical membrane growth. The Drosophila embryonic tracheal network is an excellent model to study these processes. Here, we show that the transcriptional co-activator of the Hippo pathway, Yorkie (YAP in vertebrates), plays distinct roles in the developing Drosophila airways. Yorkie exerts a cytoplasmic function by binding Drosophila Twinstar, the orthologue of the vertebrate actin-severing protein Cofilin, to regulate F-actin levels and apical cell membrane size, which are required for proper tracheal tube elongation. Second, Yorkie controls water-tightness of tracheal tubes by transcriptional regulation of the enzyme{delta} -aminolevulinate synthase (Alas). We conclude that Yorkie has a dual role in tracheal development to ensure proper tracheal growth and functionality. Short SummaryThis work identified an alternative role of the transcriptional co-activator Yorkie (Yki) in controlling water impermeability and tube size of the developing Drosophila airways. Tracheal impermeability is triggered by Yki-mediated transcriptional regulation of{delta} -aminolevulinate synthase, Alas, whereas tube elongation is controlled by binding of Yki to the actin severing factor Twinstar.

developmental biology↗