The function of α-Catenin mechanosensing in tissue morphogenesis DOI Creative Commons
Luka Sheppard, Ulrich Tepaß

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Сен. 9, 2021

Abstract α-catenin couples the cadherin-catenin complex to actin cytoskeleton. The mechanosensitive M region undergoes conformational changes upon application of force recruit binding partners. Here, we took advantage tension landscape in Drosophila embryo define three different states mechanosensing support cell adhesion. Low, medium, and high contacts showed region-dependent low, levels Vinculin Ajuba recruitment. In contrast, Afadin/Canoe acts parallel at bicellular low medium junctions, but requires an interaction with for its tension-sensitive enrichment high-tension tricellular junctions. Individual domains make contributions adhesion through their impact on partner recruitment, redundancies function Afadin/Canoe. Our data argue that partners are part a cooperative partially redundant, mechanoresponsive network supports AJs remodelling during morphogenesis.

Язык: Английский

Adherens junction: the ensemble of specialized cadherin clusters DOI Creative Commons
Sergey M. Troyanovsky

Trends in Cell Biology, Год журнала: 2022, Номер 33(5), С. 374 - 387

Опубликована: Сен. 17, 2022

Язык: Английский

Процитировано

45
Rap1 coordinates cell-cell adhesion and cytoskeletal reorganization to drive collective cell migration in vivo DOI Creative Commons
Katheryn E. Rothenberg, Yujun Chen, Jocelyn A. McDonald

и другие.

Current Biology, Год журнала: 2023, Номер 33(13), С. 2587 - 2601.e5

Опубликована: Май 26, 2023

Язык: Английский

Процитировано

22
Zyxin contributes to coupling between cell junctions and contractile actomyosin networks during apical constriction DOI Creative Commons
Mark M. Slabodnick, Sophia Tintori, Mangal Prakash

и другие.

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

Процитировано

12
The α-Catenin mechanosensing M region is required for cell adhesion during tissue morphogenesis DOI Creative Commons
Luka Sheppard, David Green, Gerald Lerchbaumer

и другие.

The Journal of Cell Biology, Год журнала: 2022, Номер 222(2)

Опубликована: Дек. 15, 2022

α-Catenin couples the cadherin-catenin complex to actin cytoskeleton. The mechanosensitive M region undergoes conformational changes upon application of force recruit interaction partners. Here, we took advantage tension landscape in Drosophila embryo define three different states mechanosensing support cell adhesion. Low-, medium-, and high-tension contacts showed a corresponding recruitment Vinculin Ajuba, which was dependent on region. In contrast, Afadin homolog Canoe acts parallel at bicellular low- medium-tension junctions but requires an with for its tension-sensitive enrichment tricellular junctions. Individual domains make contributions adhesion through their impact partner recruitment, redundancies function Canoe. Our data argue that partners are part cooperative partially redundant mechanoresponsive network supports AJs remodeling during morphogenesis.

Язык: Английский

Процитировано

17
Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis DOI Creative Commons
Noah J. Gurley,

Rachel A. Szymanski,

Robert H. Dowen

и другие.

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

Процитировано

10
Powering morphogenesis: multiscale challenges at the interface of cell adhesion and the cytoskeleton DOI
Rodrigo Fernández‐González, Mark Peifer

Molecular Biology of the Cell, Год журнала: 2022, Номер 33(8)

Опубликована: Июль 1, 2022

Among the defining features of animal kingdom is ability cells to change shape and move. This underlies embryonic postembryonic development, tissue homeostasis, regeneration, wound healing. Cell motility require linkage cell’s force-generating machinery plasma membrane at cell–cell cell–extracellular matrix junctions. Connections actomyosin cytoskeleton adherens junctions need be both resilient dynamic, preventing disruption during dramatic events morphogenesis. In past decade, new insights radically altered earlier simple paradigm that suggested linear via cadherin–catenin complex as molecular mechanism junction–cytoskeleton interaction. this Perspective we provide a brief overview our current state knowledge then focus on selected examples highlighting what view major unanswered questions in field approaches offer exciting multiple scales from atomic structure mechanics.

Язык: Английский

Процитировано

16
De novo apical domain formation inside the Drosophila adult midgut epithelium DOI Creative Commons
Jia Chen, Daniel St Johnston

eLife, Год журнала: 2022, Номер 11

Опубликована: Сен. 28, 2022

In the adult Drosophila midgut, basal intestinal stem cells give rise to enteroblasts that integrate into epithelium as they differentiate enterocytes. Integrating must generate a new apical domain and break through septate junctions between neighbouring enterocytes, while maintaining barrier function. We observe form an membrane initiation site (AMIS) when reach junction Cadherin clears from surface space appears above enteroblast. New then laterally with enterocytes AMIS develops below enterocyte junction. The enteroblast therefore forms pre-assembled compartment before it has free in contact gut lumen. Finally, disassembles enteroblast/pre-enterocyte reaches lumen fully formed brush border. process of integration resembles formation mammalian epithelial cysts, highlighting similarities fly midgut epithelia.

Язык: Английский

Процитировано

15
Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature DOI Creative Commons
Rui Gong, Matthew J. Reynolds, Xiaoyu Sun

и другие.

Science Advances, Год журнала: 2025, Номер 11(7)

Опубликована: Фев. 14, 2025

The E-cadherin–β-catenin–αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical and auxiliary binding partners converge stabilize cadherin-catenin complex’s inherently weak actin filaments (F-actin) through unclear mechanisms. Here, we show that afadin’s coiled-coil (CC) domain vinculin synergistically enhance F-actin engagement. cryo–electron microscopy (cryo-EM) structure an E-cadherin–β-catenin–αE-catenin–vinculin–afadin-CC supra-complex bound reveals afadin-CC bridges adjacent αE-catenin actin-binding domains along filament, stabilizing flexible segments implicated in mechanical regulation. These cooperative contacts promote formation clusters F-actin. Additionally, cryo-EM variability analysis links individual strands nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates mechanistic framework by which afadin tune complex–cytoskeleton coupling support AJ function varying regimes.

Язык: Английский

Процитировано

0
Actin crosslinking is required for force sensing at tricellular junctions DOI Creative Commons
Nilay Taneja, Malak Moubarak,

Meriel J. McGovern

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

Mechanical forces are essential for tissue morphogenesis, but risk causing ruptures that could compromise function. In epithelial tissues, adherens junctions withstand the drive morphogenesis by recruiting proteins stabilize cell adhesion and reinforce connections to actin cytoskeleton under tension. However, how junctional networks respond in vivo is not well understood. Here we show crosslinker Fimbrin recruited tricellular tension plays a central role amplifying actomyosin contractility stabilizing adhesion. Loss of results failure reorganize an inability enhance myosin-II activity recruit junction-stabilizing response force, disrupting Conversely, increasing constitutively activates force-response pathways, aberrantly These demonstrate Fimbrin-mediated crosslinking step modulating dynamics reinforcing during remodeling.

Язык: Английский

Процитировано

0
Afadin loss induces breast cancer metastasis through destabilisation of E‐cadherin to F‐actin linkage DOI Creative Commons
Max A. K. Rätze,

Lotte Enserink,

Noboru Ishiyama

и другие.

The Journal of Pathology, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

Abstract Afadin is a multimodal scaffolding protein with essential functions in cell–cell adhesion. Although its loss of expression has been linked to breast cancer invasion and metastasis, the underlying mechanisms driving tumour progression upon mutational ( AFDN ) cancers remains unclear. In current study we identified somatic frameshift mutation p .Lys630fs) an invasive sample that coincides expression. Functional studies E‐cadherin‐expressing cells show leads immature aberrant adherens junction (AJ) formation. The lack AJ maturation results noncohesive cellular phenotype accompanied by Actomyosin‐dependent anoikis resistance, which are classical hallmarks single‐cell invasion. Reconstitution experiments using truncates proper F‐actin organisation epithelial adhesion critically depend on Coiled‐Coil domain but not designated C‐terminal binding domain. Mouse xenograft based cell lines primary patient‐derived organoids demonstrate induces lobular‐type phenotypes overt dissemination lungs peritoneum. short, metastasis suppressor for through stabilisation mechanical E‐cadherin outside‐in link. © 2025 Author(s). Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Язык: Английский

Процитировано

0