Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions

Biology Open, Год журнала: 2025, Номер 14(2)

Опубликована: Янв. 30, 2025

The network of proteins at the interface between cell-cell adherens junctions and actomyosin cytoskeleton provides robust yet dynamic connections that facilitate cell shape change motility. While this was initially thought to be a simple linear connection via classic cadherins their associated catenins, we now have come appreciate many more are involved, providing robustness mechanosensitivity. Defining full set in remains key objective our field. Proximity proteomics means define these networks. Mammalian Afadin its Drosophila homolog Canoe parts protein network, facilitating diverse changes during gastrulation other events embryonic morphogenesis. Here report results several proximity screens, defining neighborhood both N- C-termini mammalian premier epithelial model, MDCK cells. We compare with previous screens done types, efforts junctional proteins. These reveal value multiple neighbors offer interesting insights into overlap composition different junctions.

Язык: Английский

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Feedback between mechanosensitive signaling and active forces governs endothelial junction integrity

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Ноя. 19, 2022

The formation and recovery of gaps in the vascular endothelium governs a wide range physiological pathological phenomena, from angiogenesis to tumor cell extravasation. However, interplay between mechanical signaling processes that drive dynamic behavior endothelial cells is not well understood. In this study, we propose chemo-mechanical model investigate regulation junctions as dependent on feedback actomyosin contractility, VE-cadherin bond turnover, actin polymerization, which mediate forces exerted cell-cell interface. Simulations reveal active tension can stabilize cadherin bonds, but excessive RhoA dissociation junction failure. While polymerization aids gap closure, high levels Rac1 induce weakening. Combining modeling framework with experiments, our predicts influence pharmacological treatments state identifies critical balance expression required maintain stability. Our proposed help guide development therapeutics target Rho family GTPases downstream processes.

Язык: Английский

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Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration

eLife, Год журнала: 2022, Номер 11

Опубликована: Сен. 26, 2022

For a group of cells to migrate together, each cell must couple the polarity its migratory machinery with that other in cohort. Although collective migrations are common animal development, little is known about how protrusions coherently polarized among groups migrating epithelial cells. We address this problem migration follicular

Язык: Английский

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Curvature-Induced Cell Rearrangements in Biological Tissues

Physical Review Letters, Год журнала: 2023, Номер 130(10)

Опубликована: Март 6, 2023

On a curved surface, epithelial cells can adapt to geometric constraints by tilting and exchanging their neighbors from apical basal sides, known as an apico-basal topological transition 1 (AB-T1). The relationship between cell tilt, AB-T1s, tissue curvature still lacks unified understanding. Here, we propose general framework for packing in environments explain the formation of AB-T1s perspective strain anisotropy. We find that steep gradients lead induce AB-T1s. Alternatively, pressure differences across drive regions large two mechanisms compete determine impact geometry mechanics on optimized rearrangements three dimensions.

Язык: Английский

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Multivalent interactions make adherens junction–cytoskeletal linkage robust during morphogenesis

The Journal of Cell Biology, Год журнала: 2021, Номер 220(12)

Опубликована: Ноя. 11, 2021

Embryogenesis requires cells to change shape and move without disrupting epithelial integrity. This robust, responsive linkage between adherens junctions the actomyosin cytoskeleton. Using Drosophila morphogenesis, we define molecular mechanisms mediating junction-cytoskeletal explore role of mechanosensing. We focus on linker Canoe, a multidomain protein. engineered canoe locus how its domains mediate mechanism action. To our surprise, PDZ FAB domains, which thought connected F-actin, are not required for viability or mechanosensitive recruitment under tension. The domain stabilizes experiencing elevated force, but in absence, most recover, suggesting redundant interactions. In contrast, Rap1-binding RA critical all Cno functions enrichment at supports model junctional robustness derives from large protein network assembled via multivalent interactions, with proteins nodes some node connections more than others.

Язык: Английский

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Zyxin contributes to coupling between cell junctions and contractile actomyosin networks during apical constriction

PLoS Genetics, Год журнала: 2023, Номер 19(3), С. e1010319 - e1010319

Опубликована: Март 28, 2023

One of the most common cell shape changes driving morphogenesis in diverse animals is constriction apical surface. Apical depends on contraction an actomyosin network cortex, but such networks have been shown to undergo continual, conveyor belt-like contractions before shrinking surface begins. This finding suggests that not necessarily triggered by networks, rather can be unidentified, temporally-regulated mechanical links between and junctions. Here, we used C . elegans gastrulation as a model seek genes contribute dynamic linkage. We found α-catenin β-catenin initially failed move centripetally with contracting cortical suggesting linkage regulated intact cadherin-catenin complexes actomyosin. proteomic transcriptomic approaches identify new players, including candidate linkers AFD-1/afadin ZYX-1/zyxin, contributing gastrulation. ZYX-1/zyxin among family LIM domain proteins transcripts become enriched multiple cells just they constriction. developed semi-automated image analysis tool it find contributes cell-cell junctions’ centripetal movement concert networks. These results several gastrulation, zyxin key protein important for effectively pull junctions inward during The transcriptional upregulation specific points one way developmental patterning spatiotemporally regulates biological mechanisms vivo Because related membrane-cytoskeleton other systems, anticipate its roles regulating this manner may conserved.

Язык: Английский

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Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts

Development, Год журнала: 2024, Номер 151(2)

Опубликована: Янв. 15, 2024

ABSTRACT Cell shape is a powerful readout of cell state, fate and function. We describe custom workflow to perform semi-automated, 3D nucleus segmentation, spherical harmonics principal components analysis distill nuclear variation into discrete biologically meaningful parameters. apply these methods analyze in the neuromast cells zebrafish lateral line system, finding that shapes vary with location identity. The distinction between hair support accounted for much variation, which allowed us train classifiers predict identity from features. Using transgenic markers subpopulations, we found subtypes had different each other. To investigate how loss type altered distributions, examined atoh1a mutants lack cells. mutant neuromasts lacked phenotype associated cells, but did not exhibit mutant-specific shape. Our results demonstrate utility using features characterize, compare classify living developing organism.

Язык: Английский

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Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis

PLoS ONE, Год журнала: 2023, Номер 18(8), С. e0289224 - e0289224

Опубликована: Авг. 3, 2023

One central question for cell and developmental biologists is defining how epithelial cells can change shape move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of to one another, via the cell-cell adherens junction, junctions actin myosin cytoskeleton, which generates force. The last decade revealed that these involve a multivalent network proteins, rather than simple linear pathway. We focus on Drosophila Canoe, homolog mammalian Afadin, as model underlying mechanisms. Canoe Afadin are complex, multidomain proteins share multiple domains with defined undefined binding partners. Both also long carboxy-terminal intrinsically disordered region (IDR), whose function less well defined. IDRs found in many assembled into large multiprotein complexes. have combined bioinformatic analysis use series canoe mutants early stop codons explore evolution IDR. Our reveals differ dramatically sequence properties. When we looked over shorter evolutionary time scales, identified conserved motifs. Some predicted by AlphaFold be alpha-helical, two correspond known protein interaction sites alpha-catenin F-actin. next lesions eighteen mutants, across entire coding sequence. Analysis their phenotypes consistent idea IDR, including motifs critical function. These data provide foundation further IDR

Язык: Английский

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ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism detecting alteration of septate junction integrity in Drosophila epithelial cells

eLife, Год журнала: 2024, Номер 13

Опубликована: Фев. 2, 2024

Barrier functions of proliferative epithelia are constantly challenged by mechanical and chemical constraints. How respond to cope with disturbances barrier allow tissue integrity maintenance is poorly characterised. Cellular junctions play an important role in this process intracellular traffic contribute their homeostasis. Here, we reveal that, Drosophila pupal notum, alteration the bi- or tricellular septate (SJs) triggers a mechanism two prominent outcomes. On one hand, there increase levels E-cadherin, F-actin, non-muscle myosin II plane adherens junctions. other β-integrin/Vinculin-positive cell contacts reinforced along lateral basal membranes. We found that weakening SJ integrity, caused depletion components, alters ESCRT-III/Vps32/Shrub distribution, reduces degradation instead favours recycling effect extends recycled transmembrane protein cargoes including Crumbs, its effector β-Heavy Spectrin Karst, β-integrin. propose which epithelial cells, upon sensing alterations SJ, reroute function Shrub adjust balance degradation/recycling junctional thereby compensate for junction defects maintain integrity.

Язык: Английский

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Lmo7 recruits myosin II heavy chain to regulate actomyosin contractility and apical domain size in Xenopus ectoderm

Development, Год журнала: 2022, Номер 149(10)

Опубликована: Апрель 22, 2022

ABSTRACT Apical constriction, or a reduction in size of the apical domain, underlies many morphogenetic events during development. Actomyosin complexes play an essential role constriction; however, detailed analysis molecular mechanisms is still pending. Here, we show that Lim domain only protein 7 (Lmo7), multidomain adaptor at junctions, promotes constriction Xenopus superficial ectoderm, whereas increases Lmo7-depleted cells. Lmo7 primarily localized junctions and formation dense circumferential actomyosin belt. Strikingly, binds non-muscle myosin II (NMII) recruits it to cortex. This NMII recruitment for Lmo7-mediated constriction. knockdown decreases NMIIA localization delays neural tube closure embryos. Our findings suggest serves as scaffold regulates contractility size.

Язык: Английский

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