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Tjoelker, K. K.

Publications and source records attributed to Tjoelker, K. K..

2 recordsLinked to original sources

Calcium and actomyosin pulses drive tricellular zipping to remodel epithelial cell-cell junctions and facilitate cell packing

Epithelial morphogenesis requires coordinated changes in cell geometry, neighbor cell arrangement, and cell packing to generate functional tissue architectures. However, the spatiotemporal regulation of upstream signals that drive local junctional remodeling in highly proliferative developing epithelial tissues remains unclear. Here, we characterize a new junction remodeling process, which we call "tricellular zipping". It resolves long, thin cell extensions generated by cell-division forces that terminate at transient higher-order vertices. We show that tricellular zipping facilitates epithelial cell packing in blastula-stage Xenopus laevis embryos through asymmetric displacement of a tricellular vertex and formation of a de novo bicellular interface. Similarly, we observe tricellular zipping in developing mouse embryos. Combining modeling and live imaging approaches, we find that displacement of the remodeling vertex depends on actomyosin-dependent asymmetric force generation and on enrichment of adaptor proteins coupling actomyosin to junctions, which enables effective force transmission. In contrast, the stationary vertex remains close to mechanical equilibrium and therefore undergoes no net displacement. Furthermore, we find that calcium flashes drive the localized, pulsatile actomyosin contractility required for efficient tricellular zipping. Extending our observations, we show that disrupting transient calcium signaling also affects cell packing in Drosophila embryos, thereby impairing mesoderm internalization. Overall, by combining multidisciplinary and multisystem approaches, we uncover a new mode of junctional remodeling and highlight the importance of spatiotemporally regulated calcium signaling in driving local junctional rearrangements to facilitate morphogenesis.

cell biology↗

Zyxin and LPP differ in their sensing of strained actin filaments at tricellular junctions

The actomyosin cytoskeleton plays important roles in cell-cell adhesion by generating and responding to forces. Actin-binding proteins support actomyosin networks by reinforcing actin filaments, promoting actin remodeling, and transmitting forces to transmembrane adhesion proteins. One family of actin-binding proteins, LIM domain-containing proteins, is recruited to strained actin filaments. Here, we investigate two members of the LIM domain family, Zyxin and Lipoma-Preferred Partner (LPP), using the embryonic epithelium of Xenopus laevis, where actin-associated cell-cell junctions connect cells to promote tissue integrity and barrier function. Specifically, we compare Zyxin and LPP's response to increased tension at tricellular junctions (TCJs), sites of heightened mechanical strain within the tissue. Upon increased tension, Zyxin and LPP mechanoaccumulate to different extents relative to F-actin, suggesting distinct mechanisms. Our results demonstrate that Zyxin's and LPP's LIM domain-containing regions (LCRs) are sufficient for mechanoaccumulation as well as responsible for the difference in mechanoaccumulation, while their N-termini play a regulatory role in their mechanosensitive responses. Docking simulations show that a hydrophobic interaction between the LCR and the "crack site" that forms in F-actin filaments under high force may underlie the LCR's sensing of strained F-actin. Additionally, the docking simulations reveal that previously-identified conserved residues are present at the binding interface. Mutations of conserved residues in Zyxin or LPP reduce the extent of mechanoaccumulation at TCJs, supporting the docking prediction. Together, this study advances our understanding of Zyxin and LPP's sensing of strained actin at TCJs under mechanical challenge.

cell biology↗