The Interaction of Mechanics and the Hippo Pathway in Drosophila melanogaster DOI Open Access

Jia Gou,

Tianhao Zhang, Hans G. Othmer

и другие.

Cancers, Год журнала: 2023, Номер 15(19), С. 4840 - 4840

Опубликована: Окт. 3, 2023

Drosophila melanogaster has emerged as an ideal system for studying the networks that control tissue development and homeostasis and, given similarity of pathways involved, controlled uncontrolled growth in mammalian systems. The signaling used patterning wing disc are well known result emergence interaction these with Hippo pathway, which plays a central role controlling cell proliferation apoptosis. Mechanical effects another major factor growth, but far less is about how they exert their control. Herein, we develop mathematical model integrates mechanical interactions between cells, occur via adherens tight junctions, intracellular actin network pathway so to better understand cell-autonomous non-autonomous response forces.

Язык: Английский

Mechanism of the cadherin–catenin F-actin catch bond interaction DOI Creative Commons
Amy Wang, Alexander R. Dunn, William I. Weis

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Авг. 1, 2022

Mechanotransduction at cell–cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, weak in solution but strengthened applied force due force-dependent transitions between strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that bond property principally resides αE-catenin domain (ABD). Consistent our previously proposed model, deletion first helix five-helix ABD bundle enables stable interactions F-actin under minimal are well single-state slip even when complexed β-catenin E-cadherin. Our data argue conserved mechanism adhesion proteins structurally similar ABDs. We also demonstrate stably bound strengthens load-dependent neighboring complex presence other domains weakens this effect. These results mechanistic insight cooperative cadherin–catenin which regulate dynamic cytoskeletal linkages epithelial tissues.

Язык: Английский

Процитировано

46
Mechanotransduction: Forcing a change in metabolism DOI Creative Commons
Logan W. Dawson, Nicholas M. Cronin, Kris A. DeMali

и другие.

Current Opinion in Cell Biology, Год журнала: 2023, Номер 84, С. 102219 - 102219

Опубликована: Авг. 29, 2023

Язык: Английский

Процитировано

9
Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction DOI Creative Commons

Nicole Morales‐Camilo,

Jingzhun Liu,

Manuel J. Ramírez

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 5, 2024

Abstract Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at AJs. However, canonical model fails to explain force when essential proteins module are mutated or missing. Here, we demonstrate that, in absence α-catenin, β-catenin can directly functionally interact with vinculin its open conformation, bearing physiological forces. Furthermore, found that prevent autoinhibition presence α-catenin by occupying vinculin´s head-tail interaction site, thus preserving capability. Taken together, our findings suggest a multi-step process AJs, where alternatively cooperatively vinculin. This graded responses needed maintain mechanical homeostasis and, importantly, unveils force-bearing mechanism involving extended potentially underlying enabling collective invasion metastatic cells lacking α-catenin.

Язык: Английский

Процитировано

3
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
Principles and regulation of mechanosensing DOI
Stefano Sala, Alexia Caillier, Patrick W. Oakes

и другие.

Journal of Cell Science, Год журнала: 2024, Номер 137(18)

Опубликована: Сен. 15, 2024

ABSTRACT Research over the past two decades has highlighted that mechanical signaling is a crucial component in regulating biological processes. Although many processes and proteins are termed ‘mechanosensitive’, underlying mechanisms involved mechanosensing can vary greatly. Recent studies have also identified behaviors be regulated independently of applied force. This important finding major implications for our understanding downstream mechanotransduction, process by which signals converted into biochemical signals, as it offers another layer regulatory control these pathways. In this Review, we discuss different molecular cellular mechanosensing, how their effects on mechanotransduction. Together, discussions provide an perspective cells tissues ways they sense interpret signals.

Язык: Английский

Процитировано

3
PDZ Domains from the Junctional Proteins Afadin and ZO-1 Act as Mechanosensors DOI Open Access
Vipul T. Vachharajani, Matthew DeJong, Soumya Dutta

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 24, 2023

Abstract Intercellular adhesion complexes must withstand mechanical forces to maintain tissue cohesion while also retaining the capacity for dynamic remodeling during morphogenesis and repair. Many cell-cell contain at least one PSD95/Dlg/ZO-1 (PDZ) domain situated between molecule actin cytoskeleton. However, PDZ-mediated interactions are characteristically nonspecific, weak, transient, with multiple binding partners per PDZ domain, micromolar dissociation constants, bond lifetimes of seconds or less. Here, we demonstrate that bonds cytoskeletal adaptor protein afadin intracellular domains molecules nectin-1 JAM-A form molecular catch reinforce in response load. In contrast, PDZ3-SH3-GUK (PSG) ZO-1 becomes dramatically weaker ∼2 pN load, amount generated by single motor myosin II. Thus, physiologically relevant can exert dramatic opposite effects on stability two major linkages proteins F-actin Our data serve as force-responsive anchors complexes. More broadly, our findings suggest force may a previously unsuspected regulator hundreds PDZ-ligand present animal cells.

Язык: Английский

Процитировано

6
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.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 11, 2024

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-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, 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

2
Cross-regulations of two connected domains form a mechanical circuit for steady force transmission during clathrin-mediated endocytosis DOI Creative Commons
Yuan Ren, Jie Yang,

Barbara Fujita

и другие.

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114725 - 114725

Опубликована: Сен. 1, 2024

Mechanical forces are transmitted from the actin cytoskeleton to membrane during clathrin-mediated endocytosis (CME) in fission yeast Schizosaccharomyces pombe. End4p directly transmits force CME by binding both (through AP180 N-terminal homology [ANTH] domain) and F-actin talin-HIP1/R/Sla2p actin-tethering C-terminal [THATCH] domain). We show that 7 pN is required for stable between THATCH F-actin. also characterized a domain End4p, Rend (rod End4p), resembles R12 of talin. Membrane localization primes F-actin, force-induced unfolding at 15 terminates transmission force. mechanical properties (mechanical stability, extension, hysteresis) tuned form circuit initiation, transmission, termination membrane. The may be conserved coopted evolutionarily cell adhesion complexes.

Язык: Английский

Процитировано

1
A mechanical circuit in End4p coordinates force transmission during clathrin-mediated endocytosis DOI Creative Commons
Yuan Ren, Jie Yang,

Barbara Fujita

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 23, 2023

Abstract Mechanical forces are transmitted from the actin cytoskeleton to membrane during clathrin-mediated endocytosis (CME) in fission yeast Schizosaccharomyces pombe . The onset and termination of force transmission is tightly regulated temporally different stages CME, spatially over surface invaginated membrane. How coordinated at molecular scale unclear. An adaptor protein End4p, directly transmits by binding both (through ANTH domain) F-actin THATCH domain). We show that 8pN required for stable between F-actin. also report discovery characterization a new domain on which we named Rend ( R End 4p), resembles R12 talin. Membrane localization primes F-actin, force-induced unfolding 15pN terminates CME. mechanical properties (mechanical stability, length, hysteresis) tuned form an auto-regulated circuit initiation, Shorting leads permanent End4p association with or failure enter cycle. Mathematical modeling through Rend-THATCH connection shows input buffered narrow range towards may be conserved coopted evolutionarily cell adhesion complexes.

Язык: Английский

Процитировано

2
The Interaction of Mechanics and the Hippo Pathway in Drosophila melanogaster DOI Open Access

Jia Gou,

Tianhao Zhang, Hans G. Othmer

и другие.

Cancers, Год журнала: 2023, Номер 15(19), С. 4840 - 4840

Опубликована: Окт. 3, 2023

Drosophila melanogaster has emerged as an ideal system for studying the networks that control tissue development and homeostasis and, given similarity of pathways involved, controlled uncontrolled growth in mammalian systems. The signaling used patterning wing disc are well known result emergence interaction these with Hippo pathway, which plays a central role controlling cell proliferation apoptosis. Mechanical effects another major factor growth, but far less is about how they exert their control. Herein, we develop mathematical model integrates mechanical interactions between cells, occur via adherens tight junctions, intracellular actin network pathway so to better understand cell-autonomous non-autonomous response forces.

Язык: Английский

Процитировано

0