Biology subjects

Matsuzawa, K.

Publications and source records attributed to Matsuzawa, K..

3 recordsLinked to original sources

bioRxiv2025

A steady state pool of calcium-dependent actin is maintained by Homer and controls epithelial mechanosensation

Epithelial cells are inherently contractile and in homeostasis, tissue integrity is maintained by balancing the uneven contractile forces in neighboring cells at the cell-cell interface. By contrast, epithelial cells can utilize an imbalance in contractile force to communicate various information to induce tissue-wide response as in wound healing. Contractility is generated and processed at the apical junctional complex (AJC) by the dynamic behavior of the actin cytoskeleton. Calcium signaling can pattern cellular responses based on its reach and amplitude and the actin cytoskeleton is supported by its wide ranging effects on actin regulators. Calcium transients regulate various cell behaviors associated with actin remodeling, such as in damage response and developmental morphogenesis. Here we report that calcium maintains an adaptive pool of AJC-associated actin that is sensitive to tension and encoded by calcium dynamics. For this, the recently identified epithelial polarity module Homer-MUPP1/PatJ is required. Homer regulates calcium signaling in various tissue contexts through interaction with numerous components of the endoplasmic reticulum (ER) and plasma membrane (PM) calcium signal toolkit. Knockout of either Homer or MUPP1/PatJ attenuated tension-induced calcium response and severely disrupted wound healing migration, which is dependent on guidance input through AJC tension. We also show that Homer is integral to early embryonic neurodevelopment as its suppression causes failure of neural tube closure. Our findings highlight the critical role of localized calcium dynamics on AJC actin remodeling and cellular behavior, elucidating the means of tissue coordination through intercellular tension. Significance statementThis study uncovers a novel mechanism by which localized calcium dynamics at the apical junctional complex maintain an adaptive, tension sensitive pool of actin, regulated by the epithelial polarity scaffolds Homer and MUPP1/PatJ. Importantly, this mechanism operates without perturbing epithelial polarity, indicating a specific means to modulate tissue mechanics. By linking mechanical forces to localized calcium amplification, this module enables precise mechanosensation, coordinating collective behaviors such as epithelial wound healing and neural tube closure in Xenopus. These findings redefine our understanding of intercellular tension sensing in epithelial tissues and highlight the Homer-calcium signaling axis as a key driver of tissue morphogenesis and homeostasis, with far reaching implications for developmental biology, regenerative medicine, and neural tube defect pathogenesis.

cell biology↗

bioRxiv2025

Wounding induces preexisting multinucleated cells to survive and thrive as leader cells

Epithelial wounds are repaired through collective cell migration, a process orchestrated by a small subset of leader cells at the wound edge1-3. How these functionally distinct cells arise from an apparently homogeneous population of epithelial cells remains unclear. Here, we show that injury to cultured epithelial sheets allows the survival of multinucleated cells that are otherwise eliminated under normal conditions. We reveal that multinucleated cells preexist prior to injury and extend protrusions toward the wound, eventually adopting leader-like behaviors. These findings identify multinucleated cells as a latent reservoir for leader cell emergence. Our work highlights the inherent heterogeneity of epithelial sheets and uncovers a previously unrecognized function of multinucleated cells during wound healing.

cell biology↗

bioRxiv2023

Post-synaptic competition between calcineurin and PKA regulates mammalian sleep-wake cycles

Phosphorylation of synaptic proteins is a pivotal biochemical reaction that controls the sleep-wake cycle in mammals. Protein phosphorylation in vivo is reversibly regulated by kinases and phosphatases. In this study, we investigated a pair of kinases and phosphatases that reciprocally regulate sleep duration. Through comprehensive screening of Protein kinase A (PKA) and phosphoprotein phosphatase (PPP) family genes via the generation of 40 gene knockout mouse lines including post-natal CRISPR targeting, we identified a regulatory subunit of PKA (Prkar2b), a regulatory subunit of protein phosphatase (PP) 1 (Pppr1r9b), and catalytic and regulatory subunits of PP2B (calcineurin) (Ppp3ca and Ppp3r1) as sleep control genes. AAV-mediated stimulation of PKA and PP1/calcineurin activities confirmed PKA as a wake-promoting kinase, while PP1 and calcineurin function as sleep-promoting phosphatases. The importance of these phosphatases in sleep regulation is supported by the dramatic changes in sleep duration associated with their increased and decreased activity, ranging from approximately 17.3 hours/day (PP1 expression) to 6.7 hours/day (post-natal CRISPR targeting of calcineurin). For these phosphatases to exert their sleep-promoting effects, localization signals to the excitatory post-synapse were necessary. Furthermore, the wake-promoting effect of PKA localized to the excitatory post-synapse negated the sleep-promoting effect of calcineurin, suggesting that PKA and calcineurin construct a hierarchical phosphorylation control network for sleep regulation at excitatory post-synapses.

neuroscience↗