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Tee, Y. H.

Publications and source records attributed to Tee, Y. H..

4 recordsLinked to original sources

Redeployment of Archaeal ESCRT Systems Reveals Conserved Mechanisms Underlying Eukaryotic Complexity

Eukaryotic ESCRT complexes remodel membranes at the plasma membrane and internal compartments, yet how these systems evolved from prokaryotic precursors functioning at the cellular membrane remains unresolved. Here, we show that ESCRT-II, ESCRT-III, VPS4, and ubiquitin from Candidatus Prometheoarchaeum syntrophicum (MK-D1), an Asgard archaeon closely related to eukaryotes, are recruited to canonical ESCRT sites in human cells, including centrosomes, midbodies, nuclear envelopes, endosomes despite the absence of these structures from MK-D1 morphology. In addition to MK-D1 ESCRT II recruitment at these regions, MK-D1 ESCRT-III and VPS4 form ring assemblies at midbodies and target reforming nuclear envelope regions. Futhermore, expression of MK-D1 ESCRT modules enhances efficiency of viral budding in human cells. These findings provide direct experimental evidence that archaeal ESCRT modules integrate into diverse eukaryotic structures, supporting a model in which ancestral membrane-remodeling systems were redeployed during eukaryogenesis to organize novel internal architectures.

evolutionary biology↗

Ordering from the edge: Chiral multicellular pattern formation directed by actin self-organisation in cells

The mechanisms underlying both the establishment of mirror symmetry and deviations from it in development of bilateral multicellular organisms remain insufficiently understood. Actin cytoskeletons of individual cells exhibit intrinsic chirality, and a strong correlation exists between single-cell actin fibres chiral organisation and the collective alignment of cells confined to rectangular adhesive islands (2D-microtissues). Here, we demonstrate how multicellular chiral patterns can be inferred from the chiral behaviour of actin fibres in individual cells. By analysing chiral actin systems in cells with elliptical and semi-circular shapes, representing inner and boundary positions within 2D-microtissues, we defined the rules of chiral motile behaviour and formulated two models of cell alignment: (i) chiral rotation of inner cells and (ii) chiral tilting of boundary cells relative to island edges. In both models, neighbouring cells are also mutually aligned. Systematic variation of island area and aspect ratio, combined with dynamic observations, revealed the primary role of boundary cells. Chiral order first emerged at tissue boundaries and then propagated inward. This outside-in mechanism also explains why mirror-symmetric cell groups are difficult to achieve with uniformly chiral cells, but can be obtained either by reversing chirality in one subgroup or by enlarging the microtissue to minimise boundary influence.

biophysics↗

Actin polymerization and crosslinking drive left-right asymmetry in single cell and cell collectives

Deviations from mirror symmetry in the development of bilateral organisms are highly stereotypic and genetically predetermined, but their mechanisms are not sufficiently understood. At the cellular level, self-organization of the actin cytoskeleton results in chiral actin swirling, and cells in groups confined to micropatterns demonstrate chiral cell alignment. The relationship between individual and collective cell chirality is unclear, and molecular players involved remain essentially unidentified. Here, by screening major actin-associated proteins and deep-learning-based morphometric analysis of actin patterns, we found that knockdowns of specific actin polymerization regulators, such as mDia1, ARPC2, and cofilins 1&2, abolished chiral actin swirling, while depletion of profilin 1 and CapZ{beta}, reversed its direction in an actin crosslinker -actinin1-dependent manner. Analysis of these and other knockdowns and pharmacological treatments revealed a robust correlation between their effects on the chirality of individual cells and confined cell groups. Thus, actin-driven cell chirality may underlie tissue and organ asymmetry. One Sentence SummaryCell chirality determined by specific regulators of actin polymerization drives left-right asymmetry emergence in cell groups

cell biology↗

Actin cytoskeleton self-organization in single epithelial cells and fibroblasts under isotropic confinement

We systematically investigated the principles of actin cytoskeleton self-organization in two cell types, fibroblasts and epitheliocytes, by confining isolated cells on isotropic adhesive islands of varying size. In fibroblasts, we previously described that an initially circular pattern of circumferential actin dynamically evolves into a radial pattern of actin bundles that spontaneously transforms into a chiral pattern, before finally producing parallel linear stress fibres. We now show that progression from circular to chiral actin patterns depends on cell projected area and rarely occurs on small islands. Epitheliocytes however, did not exhibit succession through all the actin patterns described above even on large islands. Upon confinement, the actin cytoskeleton in non-keratinocyte epitheliocytes is arrested at the circular stage, while in keratinocytes it can progress as far as the radial pattern but still cannot break symmetry. Epithelial-mesenchymal transition pushed actin cytoskeleton development from circular towards radial patterns but remains insufficient to cause chirality. Surprisingly, small doses of G-actin sequestering drug, latrunculin A, induced chiral swirling in keratinocytes. During this swirling, keratin filaments follow actin and also demonstrate chiral swirling movement. Elimination of the keratin network by genetic silencing of Type II keratins, however, did not affect the self-organization of the actin cytoskeleton.

cell biology↗