Systematic analysis of RhoGEF/GAP localizations uncovers regulators of mechanosensing and junction formation during epithelial cell division DOI Creative Commons
Florencia di Pietro, Mariana Osswald, José M. De las Heras

et al.

Current Biology, Journal Year: 2023, Volume and Issue: 33(5), P. 858 - 874.e7

Published: Feb. 13, 2023

Cell proliferation is central to epithelial tissue development, repair, and homeostasis. During cell division, small RhoGTPases control both actomyosin dynamics cell-cell junction remodeling faithfully segregate the genome while maintaining polarity integrity. To decipher mechanisms of RhoGTPase spatiotemporal regulation during we generated a transgenic fluorescently tagged library for 48 Drosophila Rho guanine exchange factors (RhoGEFs) GTPase-activating proteins (GAPs), systematically characterized their endogenous distributions by time-lapse microscopy. Therefore, unveiled candidate regulators interplay between junctional division. Building on these findings, established that conserved RhoGEF Cysts RhoGEF4 play sequential distinct roles couple cytokinesis with de novo formation. ring contraction, via Rho1 participates in neighbor mechanosensing response, promoting daughter-daughter membrane juxtaposition preparation Subsequently upon midbody formation, Rac acts dividing ensure withdrawal neighboring membranes, thus controlling length arrangements cytokinesis. Altogether, our findings delineate how are locally temporally activated cytokinesis, highlighting RhoGEF/GAP as key resource understand broad range biological processes regulated RhoGTPases.

Language: Английский

ERK-Mediated Mechanochemical Waves Direct Collective Cell Polarization DOI Creative Commons
Naoya Hino, Leone Rossetti,

Ariadna Marín-Llauradó

et al.

Developmental Cell, Journal Year: 2020, Volume and Issue: 53(6), P. 646 - 660.e8

Published: June 1, 2020

Language: Английский

Citations

219
The role of single-cell mechanical behaviour and polarity in driving collective cell migration DOI
Shreyansh Jain, Victoire Cachoux, Gautham Hari Narayana Sankara Narayana

et al.

Nature Physics, Journal Year: 2020, Volume and Issue: 16(7), P. 802 - 809

Published: May 4, 2020

Language: Английский

Citations

155
Adherens junctions as molecular regulators of emergent tissue mechanics DOI
Otger Campàs, Ivar Noordstra, Alpha S. Yap

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 252 - 269

Published: Dec. 13, 2023

Language: Английский

Citations

47
Cell-cell junctions as sensors and transducers of mechanical forces DOI Creative Commons
Ana Angulo‐Urarte, Tanne van der Wal, Stephan Huveneers

et al.

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2020, Volume and Issue: 1862(9), P. 183316 - 183316

Published: April 28, 2020

Epithelial and endothelial monolayers are multicellular sheets that form barriers between the 'outside' 'inside' of tissues. Cell-cell junctions, made by adherens tight junctions desmosomes, hold together these monolayers. They intercellular contacts binding their receptor counterparts on neighboring cells anchoring structures intracellularly to cytoskeleton. During tissue development, maintenance pathogenesis, encounter a range mechanical forces from themselves external systemic forces, such as blood pressure or stiffness. The molecular landscape cell-cell is diverse, containing transmembrane proteins bonds variety cytoplasmic remodel junctional connection Many junction-associated participate in mechanotransduction cascades confer cues into cellular responses allow maintain structural integrity. We will discuss force-dependent events role contact organization remodeling.

Language: Английский

Citations

128
Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics DOI Creative Commons
Srikanth Budnar, Kabir Husain, Guillermo A. Gómez

et al.

Developmental Cell, Journal Year: 2019, Volume and Issue: 49(6), P. 894 - 906.e12

Published: May 16, 2019

Language: Английский

Citations

96
Rho Flares Repair Local Tight Junction Leaks DOI Creative Commons
Rachel E. Stephenson, Tomohito Higashi,

Ivan S. Erofeev

et al.

Developmental Cell, Journal Year: 2019, Volume and Issue: 48(4), P. 445 - 459.e5

Published: Feb. 1, 2019

Language: Английский

Citations

95
Distinct RhoGEFs Activate Apical and Junctional Contractility under Control of G Proteins during Epithelial Morphogenesis DOI Creative Commons
Alain Garcia De Las Bayonas, Jean‐Marc Philippe,

Annemarie C. Lellouch

et al.

Current Biology, Journal Year: 2019, Volume and Issue: 29(20), P. 3370 - 3385.e7

Published: Sept. 12, 2019

Small RhoGTPases direct cell shape changes and movements during tissue morphogenesis. Their activities are tightly regulated in space time to specify the desired pattern of actomyosin contractility that supports This is expected stem from polarized surface stimuli signaling processing inside cells. We examined this general problem context intercalation drives extension Drosophila ectoderm. In ectoderm, G protein-coupled receptors (GPCRs) their downstream heterotrimeric proteins (Gα Gβγ) activate Rho1 both medial-apically, where it exhibits pulsed dynamics, at junctions, its activity planar polarized. However, mechanisms responsible for polarizing unclear. report distinct guanine exchange factors (GEFs) these two cellular compartments. RhoGEF2 acts uniquely medial-apical but recruited medial-apically junctions by Gα12/13-GTP, also called Concertina (Cta) Drosophila. On other hand, Dp114RhoGEF (Dp114), a newly characterized RhoGEF, required extending activates specifically junctions. Its localization restricted adherens under Gβ13F/Gγ1 control. Furthermore, junctional exerts quantitative control over polarization Rho1. Finally, we found absent mesoderm, arguing tissue-specific activity. These results clarify different compartments reveal GEFs sensitive tuning parameters remodeling epithelia.

Language: Английский

Citations

77
Interplay between Extracellular Matrix Stiffness and JAM-A Regulates Mechanical Load on ZO-1 and Tight Junction Assembly DOI Creative Commons
Alexis J. Haas, Ceniz Zihni, Artur Ruppel

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 32(3), P. 107924 - 107924

Published: July 1, 2020

Tight-junction-regulated actomyosin activity determines epithelial and endothelial tension on adherens junctions drives morphogenetic processes; however, whether or not tight themselves are under tensile stress is clear. Here, we use a sensor based ZO-1, scaffolding protein that links the junctional membrane to cytoskeleton, determine if carry mechanical load. Our data indicate ZO-1 forces acting regulated by extracellular matrix (ECM) stiffness adhesion molecule JAM-A. JAM-A depletion stimulates recruitment of p114RhoGEF/ARHGEF18, traction at focal adhesions. p114RhoGEF required for activation junction integrity stiff but soft ECM. Thus, bears load, assembly interplay between physical properties ECM adhesion-regulated signaling junctions.

Language: Английский

Citations

73
Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion DOI Creative Commons
Kinga Duszyc, Guillermo A. Gómez, Anne K. Lagendijk

et al.

Current Biology, Journal Year: 2021, Volume and Issue: 31(6), P. 1326 - 1336.e5

Published: Feb. 15, 2021

Language: Английский

Citations

64
Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling DOI Creative Commons
Saranyaraajan Varadarajan, Shahana Chumki, Rachel E. Stephenson

et al.

The Journal of Cell Biology, Journal Year: 2022, Volume and Issue: 221(4)

Published: March 7, 2022

Epithelial cell–cell junctions remodel in response to mechanical stimuli maintain barrier function. Previously, we found that local leaks tight (TJs) are rapidly repaired by local, transient RhoA activation, termed “Rho flares,” but how Rho flares regulated is unknown. Here, discovered intracellular calcium flashes and junction elongation early events the flare pathway. Both laser-induced naturally occurring TJ breaks lead at site of leaks. Additionally, induced optogenetics increases frequency, suggesting mechanically triggered. Depletion or inhibition mechanosensitive channels (MSCs) reduces amplitude diminishes sustained activation flares. MSC-dependent influx necessary global function regulating reinforcement proteins via contraction. In all, uncovered a novel role for remodeling, allowing epithelial cells repair stimuli.

Language: Английский

Citations

57