Cell signaling facilitates apical constriction by basolaterally recruiting Arp2/3 via Rac and WAVE

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(5)

Published: March 5, 2025

Apical constriction is a critical cell shape change that drives internalization and tissue bending. How precisely localized actomyosin regulators drive apical remains poorly understood. Caenorhabditis elegans gastrulation provides valuable model to address this question. The Arp2/3 complex essential in C. gastrulation. To understand how locally regulated, we imaged embryos with endogenously tagged its nucleation-promoting factors (NPFs). three NPFs-WAVE, WASP, WASH-controlled localization at distinct subcellular locations. We exploited finding study populations of found only WAVE depletion caused penetrant defects. basolaterally controlled F-actin levels near cell-cell contacts. depended on CED-10/Rac. Establishing ectopic contacts recruited Arp2/3, identifying the contact as symmetry-breaking cue for these proteins. These results suggest signaling via Rac activates basolateral makes an important contribution constriction.

Language: Английский

Classification of human actin pathological variants usingC. elegansCRISPR-generated models

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract Actin plays a crucial role in diverse physiological processes via the formation of dynamic networks that determine cellular shape and mechanical properties. De novo variants cytoskeletal β- γ-actin, encoded by human ACTB ACTG1 genes, lead to wide range rare diseases, termed Non-Muscle Actinopathies (NMA). Variants include missense, frameshift, truncating up whole gene deletions induce symptoms. So far, high clinical variability genotype-phenotype correlations NMA remain largely unresolved. To address this question, we used CRISPR insert C. elegans homologue act-2 nine de mutations identified patients. Using these animal models, performed quantitative multiscale characterisation. We uncovered variety perturbations: actin network defects at micro scale, cell scale abnormalities, morphogenesis failure, as well weaker behavioural phenotypes. Importantly, developmental observed correlates with severity patients’ Thus, provide evidence - based approach represents new way investigate mechanisms underlying physiopathology or ultimately screen for therapeutic strategies.

Language: Английский

Cell signaling facilitates apical constriction by basolaterally recruiting Arp2/3 via Rac and WAVE

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Apical constriction is a critical cell shape change that bends tissues. How precisely-localized actomyosin regulators drive apical remains poorly understood.

Language: Английский