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Sugimura, K.

Publications and source records attributed to Sugimura, K..

5 recordsLinked to original sources

Mechanical convergence in mixed populations of mammalian epithelial cell

Tissues consist of cells with different molecular and/or mechanical properties. Measuring the forces and stresses in mixed-cell populations is essential for understanding the mechanisms by which tissue development, homeostasis, and disease emerge from the cooperation of distinct cell types. However, many previous studies have primarily focused their mechanical measurements on dissociated cells or aggregates of a single-cell type, leaving the mechanics of mixed-cell populations largely unexplored. In the present study, we aimed to elucidate the influence of interactions between different cell types on cell mechanics by conducting in situ mechanical measurements on a monolayer of mammalian epithelial cells. Our findings revealed that while individual cell types displayed varying magnitudes of traction and intercellular stress before mixing, these mechanical values shifted in the mixed monolayer, becoming nearly indistinguishable between the cell types. Moreover, by analyzing a mixed-phase model of active tissues, we identified physical conditions under which such mechanical convergence is induced. Overall, the present study underscores the importance of in situ mechanical measurements in mixed-cell populations to deepen our understanding of the mechanics of multi-cellular systems.

cell biology↗

CDCA7 is a hemimethylated DNA adaptor for the nucleosome remodeler HELLS

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, characterized by hypomethylation at heterochromatin. The unique zinc-finger domain, zf-4CXXC_R1, of CDCA7 is widely conserved across eukaryotes but is absent from species that lack HELLS and DNA methyltransferases, implying its specialized relation with methylated DNA. Here we demonstrate that zf-4CXXC_R1 acts as a hemimethylated DNA sensor. The zf-4CXXC_R1 domain of CDCA7 selectively binds to DNA with a hemimethylated CpG, but not unmethylated or fully methylated CpG, and ICF disease mutations eliminated this binding. CDCA7 and HELLS interact via their N-terminal alpha helices, through which HELLS is recruited to hemimethylated DNA. While placement of a hemimethylated CpG within the nucleosome core particle can hinder its recognition by CDCA7, cryo-EM structure analysis of the CDCA7-nucleosome complex suggests that zf-4CXXC_R1 recognizes a hemimethylated CpG in the major groove at linker DNA. Our study provides insights into how the CDCA7-HELLS nucleosome remodeling complex uniquely assists maintenance DNA methylation.

molecular biology↗

Coronin-1 controls directional cell rearrangement in Drosophila wing epithelium

Directional cell rearrangement is a critical process underlying correct tissue deformation during morphogenesis. Although the involvement of F-actin regulation in cell rearrangement has been established, the role and regulation of actin binding proteins (ABPs) in this process are not well understood. In this study, we investigated the function of Coronin-1, a WD-repeat actin-binding protein, in controlling directional cell rearrangement in the Drosophila pupal wing. Transgenic flies expressing Coronin-1-EGFP were generated using CRISPR-Cas9. We observed that Coronin-1 localizes at the reconnecting junction during cell rearrangement, which is dependent on actin interacting protein 1 (AIP1), an actin disassembler and a known regulator of wing cell rearrangement. Loss of Coronin-1 function reduces cell rearrangement directionality and hexagonal cell fraction. These results suggest that Coronin-1 promotes directional cell rearrangement via its interaction with AIP1, highlighting the role of ABPs in the complex process of morphogenesis.

cell biology↗

Attachment/detachment of cortical myosin regulates cell junction exchange during cell rearrangement

Epithelial cells remodel cell adhesion and change their neighbors to shape a tissue. This cell rearrangement proceeds in three steps: the shrinkage of a junction, exchange of junctions, and elongation of the newly generated junction. Herein, by combining live imaging and physical modeling, we showed that the formation of myosin-II (myo-II) cables around the cell vertices underlies the exchange of junctions. The local and transient detachment of myo-II from the cell cortex is coupled with the junction shrinkage and elongation via an interplay between the LIM domain-containing protein Jub and the tricellular junction protein M6. Furthermore, we developed a mechanical model based on the wetting theory and clarified the way by which the physical properties of myo-II cables are integrated with the junction geometry to induce the transition between the attached and detached states and support the unidirectionality of cell rearrangement. Collectively, the present study elucidates the orchestration of geometry, mechanics and signaling for exchanging junctions.

cell biology↗

Structural basis for the unique multifaceted interaction of DPPA3 with the UHRF1 PHD finger

Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced - helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3.

biochemistry↗