Biology subjects

Pedrosa, A.

Publications and source records attributed to Pedrosa, A..

4 recordsLinked to original sources

bioRxiv2026

A myosin filament cage drives multiple aspects of mitosis unique to cells dividing within a polarized epithelium

Here we used mouse intestinal organoids expressing endogenously tagged myosin to clarify its roles in those aspects of mitosis unique to division within a polarized epithelium. Super-resolution imaging of rounded metaphase cells revealed a never-before-seen myosin filament cage that only forms in this context, exhibits apical/basal polarity, maintains roundness by resisting surrounding tissue pressure, and repositions laterally to form a contractile ring predetermined to drive planar division and asymmetric cleavage furrow progression. Attenuating cage function inhibited interkinetic nuclear migration and metaphase cell rounding, causing the division plane to shift from planar to orthogonal and resulting in organoids possessing multiple lumens. Following the apical domain marker ZO-1 showed that the new lumens originate at the interface between stacked daughter cells created by orthogonal divisions. We conclude that cells dividing within polarized epithelia create a myosin filament cage designed specifically to drive those aspects of cell division unique to their context.

cell biology↗

bioRxiv2026

Acute and Lifelong Exercise Modulate the Tumorigenic Potential of Human Lung Cancer Cells and Their Susceptibility to Cisplatin

The association between higher levels of physical activity and lower cancer risk and mortality is well established. However, a causal link is yet to be proven. Recent studies showed a decrease in the proliferation rates of cultured human cancer cells when the human serum employed to stimulate them was conditioned by acute exercise. Here, we tested the hypothesis that serum mediates some of the putative benefits of exercise on cancer through alterations to the growth pattern and susceptibility to chemotherapy agents of cancer cells. To this end, human non-small cell lung cancer (NSCLC) cells were exposed to serum from two cohorts that differed significantly on their levels of physical activity and, accordingly, cardiorespiratory fitness, but were otherwise identical (master athletes and non-exercisers), collected before and after an acute exercise intervention. Serum levels of glucose, lipids, albumin, C-reactive protein and cytokines were determined and the impact of the serum responses to acute and lifelong exercise on the above-mentioned parameters were analyzed. We found that acute exercise decreased the cells proliferation rate, yet shortened the cells lag phase after detachment, whereas lifelong exercise had the opposite effects. Significantly, we showed, for the first time, that lifelong exercise increased susceptibility to a chemotherapy agent (cisplatin), which may contribute to the decreased cancer mortality rates found among those who exercise regularly. Similar to the cellular effects, changes to serum cytokine levels - several of them linked to the senescence-associated secretory phenotype - depended on whether serum was conditioned by acute or by chronic exercise. Key pointsChronic exercise increased the in vitro susceptibility of lung cancer cells to cisplatin. Acute and chronic exercise modulated the in vitro tumorigenic potential of lung cancer cells. Effects were mediated by serological changes produced by exercise. Acute and chronic exercise had distinct impacts on serological cytokine levels.

cancer biology↗

bioRxiv2023

Myosin 10 uses its MyTH4 and FERM domains differentially to support two aspects of spindle pole biology required for mitotic spindle bipolarity

Myosin 10 (Myo10) has the ability to link actin filaments to integrin-based adhesions and to microtubules by virtue of its integrin-binding FERM domain and microtubule-binding MyTH4 domain, respectively. Here we used Myo10 knockout cells to define Myo10s contribution to the maintenance of spindle bipolarity, and complementation to quantitate the relative contributions of its MyTH4 and FERM domains. Myo10 knockout HeLa cells and mouse embryo fibroblasts (MEFs) both exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that the primary driver of spindle multipolarity in knockout MEFs and knockout HeLa cells lacking supernumerary centrosomes is pericentriolar material (PCM) fragmentation, which creates y-tubulin-positive acentriolar foci that serve as additional spindle poles. For HeLa cells possessing supernumerary centrosomes, Myo10 depletion further accentuates spindle multipolarity by impairing the clustering of the extra spindle poles. Complementation experiments show that Myo10 must interact with both integrins and microtubules to promote PCM/pole integrity. Conversely, Myo10s ability to promote the clustering of supernumerary centrosomes only requires that it interact with integrins. Importantly, images of Halo-Myo10 knock-in cells show that the myosin localizes exclusively within adhesive retraction fibers during mitosis. Based on these and other results, we conclude that Myo10 promotes PCM/pole integrity at a distance, and that it facilitates supernumerary centrosome clustering by promoting retraction fiber-based cell adhesion, which likely provides an anchor for the microtubule-based forces driving pole focusing.

cell biology↗

bioRxiv2022

Myosin 10 supports mitotic spindle bipolarity by promoting PCM integrity and supernumerary centrosome clustering

Myosin 10 (Myo10) is a member of the MyTH4/FERM domain family of unconventional, actin-based motor proteins. Studies have implicated Myo10 in supporting cell adhesion via its integrin-binding FERM domain, and spindle positioning and spindle pole integrity via its microtubule-binding MyTH4 domain. Here we characterized Myo10s contribution to mitosis using Myo10 knockout HeLa cells and MEFs isolated from a Myo10 knockout mouse. Most notably, both of these knockout cells exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that the primary driver of spindle multipolarity in knockout MEFs and knockout HeLa cells lacking supernumerary centrosomes is PCM fragmentation, which creates y-tubulin-positive, centriole-negative microtubule asters that serve as additional spindle poles. For HeLa cells possessing supernumerary centrosomes, Myo10 depletion further accentuates spindle multipolarity by impairing centrosome clustering. These results argue, therefore, that Myo10 supports spindle bipolarity by maintaining PCM integrity in both normal and cancer cells, and by promoting supernumerary centrosome clustering in cancer cells. Finally, we present evidence that the defect in spindle pole integrity in Myo10 knockout cells is likely due to a defect in pole stability rather than pole maturation, and that Myo10 promotes supernumerary centrosome clustering at least in part by promoting cell adhesion during mitosis.

cell biology↗