ORCID Profile
0000-0003-0292-3506
Current Organisation
University of Queensland
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Publisher: Cold Spring Harbor Laboratory
Date: 09-05-2019
DOI: 10.1101/632802
Abstract: Mechanical tension governs epithelial morphogenesis and homeostasis, but its regulation remains poorly understood. Tension is commonly contractile, arising when the actomyosin cortices of cells are mechanically coupled together by cadherin adhesion. Here we report that caveolae control levels of epithelial tension and show that this is necessary for oncogene-transfected cells to be eliminated by apical extrusion. Depletion of caveolin-1 (CAV1) in the surrounding epithelium, but not in the oncogene-expressing cells, blocked extrusion leading to the retention and proliferation of transformed cells within the monolayer. Tensile stress was aberrantly elevated in CAV1-depleted monolayers due to elevated levels of phosphoinositide-4,5-bisphosphate (PtdIns(4,5) P 2 ) causing increased recruitment of the formin, FMNL2. Oncogenic extrusion was restored to CAV1-deficient monolayers when tension was corrected by depleting FMNL2, blocking PtdIns(4,5) P 2 , or disabling the interaction between FMNL2 and PtdIns(4,5) P 2 . Thus, by controlling lipid signalling to the actin cytoskeleton, caveolae regulate mechanical tension for epithelial homeostasis.
Publisher: eLife Sciences Publications, Ltd
Date: 18-10-2021
DOI: 10.7554/ELIFE.67915
Abstract: Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here, we focus on understanding cellular mechanisms for elongation using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this locoregional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles that were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the extracellular matrix, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry breaking and elongation. This required β1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating locoregional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
Publisher: Elsevier BV
Date: 03-2023
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.TCB.2017.02.003
Abstract: Actin filaments and associated proteins undergo wave-like movement in various cell types. Recent studies with cutting-edge analyses, including live-cell imaging, biophysical monitoring and manipulation, and mathematical modeling, have highlighted roles of 'actin waves' in cellular protrusion, polarization, and migration. The prevailing models to explain the wave-like dynamics of actin filaments involve an activator-inhibitor mechanism. In addition, axonal actin waves migrate by means of directional assembly and disassembly of membrane-anchored actin filaments, and thus represent a new type of machinery that translocates their component molecules to the cell edge. Here, we review recent advances in our understanding of the generation, mobility, and functions of actin waves, and discuss how actin waves may self-organize into the molecular machinery underlying cell morphogenesis.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.CELREP.2015.06.048
Abstract: Actin and actin-associated proteins migrate within various cell types. To uncover the mechanism of their migration, we analyzed actin waves, which translocate actin and actin-associated proteins along neuronal axons toward the growth cones. We found that arrays of actin filaments constituting waves undergo directional assembly and disassembly, with their polymerizing ends oriented toward the axonal tip, and that the lateral side of the filaments is mechanically anchored to the adhesive substrate. A combination of live-cell imaging, molecular manipulation, force measurement, and mathematical modeling revealed that wave migration is driven by directional assembly and disassembly of actin filaments and their anchorage to the substrate. Actin-associated proteins co-migrate with actin filaments by interacting with them. Furthermore, blocking this migration, by creating an adhesion-free gap along the axon, disrupts axonal protrusion. Our findings identify a molecular mechanism that translocates actin and associated proteins toward the cell's leading edge, thereby promoting directional cell motility.
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.CELREP.2021.109130
Abstract: Dendritic spines constitute the major compartments of excitatory post-synapses. They undergo activity-dependent enlargement, which is thought to increase the synaptic efficacy underlying learning and memory. The activity-dependent spine enlargement requires activation of signaling pathways leading to promotion of actin polymerization within the spines. However, the molecular machinery that suffices for that structural plasticity remains unclear. Here, we demonstrate that shootin1a links polymerizing actin filaments in spines with the cell-adhesion molecules N-cadherin and L1-CAM, thereby mechanically coupling the filaments to the extracellular environment. Synaptic activation enhances shootin1a-mediated actin-adhesion coupling in spines. Promotion of actin polymerization is insufficient for the plasticity the enhanced actin-adhesion coupling is required for polymerizing actin filaments to push against the membrane for spine enlargement. By integrating cell signaling, cell adhesion, and force generation into the current model of actin-based machinery, we propose molecular machinery that is sufficient to trigger the activity-dependent spine structural plasticity.
Publisher: Cold Spring Harbor Laboratory
Date: 28-02-2021
DOI: 10.1101/2021.02.28.433274
Abstract: Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required β1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
Publisher: Wiley
Date: 25-11-2020
Publisher: Elsevier BV
Date: 07-2020
Publisher: eLife Sciences Publications, Ltd
Date: 07-09-2021
Publisher: Proceedings of the National Academy of Sciences
Date: 26-02-2018
Abstract: Cell migration directed by substrate-bound chemical cues is called haptotaxis. This study shows that grip and slip between the cell adhesion molecule (CAM) L1-CAM and the adhesive substrates, which occur asymmetrically under the growth cone, direct growth cone migration mediated by laminin. This mechanism is disrupted in a human patient of L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia. These findings provide a conceptual framework for understanding the regulation and dysregulation of cell migration on the bases of force generation.
Publisher: Wiley
Date: 07-01-2020
DOI: 10.1111/TRA.12721
Abstract: By happy chance, the founding of Traffic in 1999 coincided with a clutch of reports that documented the endocytosis and recycling of classical cadherin adhesion receptors. This stimulated a concerted effort to elucidate the molecular regulation of cadherin endocytosis and to identify its functional implications. In particular, endocytosis provided new perspectives to understand how cadherins are modulated during tissue morphogenesis. In this short article, we consider some of what we have learnt about this problem and identify open questions for future research.
No related grants have been discovered for Hiroko Kambe.