Biology subjects

Capalbo, L.

Publications and source records attributed to Capalbo, L..

4 recordsLinked to original sources

bioRxiv2026

Time-dependent effect of fluoride on caries lesions development in a rat caries model

Since model dose-response is critical when assessing caries lesion development over time, this study evaluated the influence of fluoride dose and treatment duration on caries progression in a rat caries model. Streptococcus mutans-infected Sprague-Dawley rats were treated with deionized water, 226 ppm F-, or 2,260 ppm F- twice daily for 3, 4, or 5 weeks. Caries lesions were assessed using Larson's modification of the Keyes scoring system and complemented by micro-computed tomography (microCT). Intraoral fluoride availability, serum and bone fluoride concentrations and microbial counts were also determined. Fluoride reduced caries severity in a dose- and time-dependent manner. While early enamel lesions were detected in all groups, extensive dentine lesions increased over time, in a dose-dependent manner, in the control and 226 ppm F- groups, and were not observed in the 2,260 ppm F- group after 5 weeks. Intraoral and bone fluoride availability increased significantly with fluoride concentration and treatment duration, whereas serum fluoride levels reflected fluoride dose instead of treatment duration. MicroCT-derived enamel volume correlated negatively with both total and extensive caries scores, supporting its utility as an objective measure of lesion severity. In conclusion, extending model length from 3 to 5 weeks increased the severity of caries lesions in a dose-dependent manner. Fluoride intraoral availability and bone fluoride also demonstrated a dose and time-dependent response.

pathology↗

bioRxiv2025

Coordinated regulation of Citron kinase by CDK1 and Aurora B regulates midbody formation and stability

Many cell division events are regulated by protein phosphorylation, which can result from cross-talk mechanisms among mitotic kinases and phosphatases that have yet to be fully elucidated. Here, we report the characterization of a novel cross-talk mechanism by which CDK1 and Aurora B (AURKB) kinases regulate the distribution and interactions of Citron kinase (CIT-K). We show that CDK1 and AURKB phosphorylate two serine residues, S440 and S699, located adjacent to or within CIT-K coiled coil domain. S440 and S699 temporal phosphorylation profiles reflect the activity of the kinases responsible for their phosphorylation. Functional analyses using phospho mutants indicate that S699 phosphorylation is important for CIT-K localization and successful cytokinesis, while perturbing S440 phosphorylation leads to abnormal midbody formation and accumulation of post-mitotic midbody remnants (MBRs). Furthermore, we found that phosphorylation at either residue reduces the ability of CIT-K to interact with its midbody partners AURKB, KIF14 and KIF23/MKLP1. Together, our findings indicate that phosphorylation of CIT-K by CDK1 and AURKB regulates midbody formation and MBR stability by controlling the association of CIT-K with its partners. They expand our understanding of the mechanisms that regulate abscission and can lead to further insights into the role of MBRs in post-mitotic events.

cell biology↗

bioRxiv2020

Phosphorylation by Aurora B kinase regulates caspase-2 activity and function

Mitotic catastrophe (MC) is an important oncosuppressive mechanism that serves to eliminate cells that become polyploid or aneuploidy due to aberrant mitosis. Previous studies have demonstrated that the activation and catalytic function of caspase-2 are key steps in MC to trigger apoptosis and/or cell cycle arrest of mitotically defective cells. However, the molecular mechanisms that regulate caspase-2 activation and its function are unclear. Here we identify six new phosphorylation sites in caspase-2 and show that a key mitotic kinase, Aurora B kinase (AURKB), phosphorylates caspase-2 at the highly conserved residue S384. We demonstrate that phosphorylation at S384 blocks caspase-2 catalytic activity and apoptosis function in response to mitotic insults, without affecting caspase-2 dimerisation. Moreover, molecular modelling suggests that phosphorylation at S384 may affect substrate binding by caspase-2. We propose that caspase-2 S384 phosphorylation by AURKB is a key mechanism that controls caspase-2 activation during mitosis.

cell biology↗

bioRxiv2019

The midbody interactome reveals new unexpected roles for PP1 phosphatases in cytokinesis

The midbody is an organelle assembled at the intercellular bridge that connects the two daughter cells at the end of mitosis. It is composed of a multitude of proteins, organized in a precise and stereotyped pattern, that control the final separation of the daughter cells and prevent incorrect genome segregation. Furthermore, recent evidence indicates that the midbody is involved in many other important processes, including cell fate, pluripotency, apical-basal polarity, tissue organization, and cilium and lumen formation. Understanding the regulation and interactions of midbody proteins is therefore essential to unravel how this organelle executes its multiple functions. Here, we report the first experimentally-based characterization of the intricate midbody protein-protein interaction network (interactome), which identifies a plethora of novel interactions and provides an extremely valuable resource for dissecting the multiple roles of the midbody. Initial analysis of this interactome already revealed that PP1{beta}-MYPT1 phosphatase regulates microtubule dynamics in late cytokinesis and de-phosphorylates the kinesin component MKLP1/KIF23 of the centralspindlin complex, a key cytokinesis regulator. This de-phosphorylation antagonizes Aurora B kinase in order to modify the functions of centralspindlin and its interactions in late cytokinesis. Our findings expand the repertoire of PP1 functions during mitosis and indicate that spatiotemporal changes in the distribution of kinases and counteracting phosphatases finely tune the activity of cytokinesis proteins.

cell biology↗