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Cell signaling facilitates apical constriction by basolaterally recruiting Arp2/3 via Rac and WAVE
Pu Zhang1,2, Taylor N Medwig-Kinney1, Eleanor A Breiner1
1Biology Department, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Biorxiv : the Preprint Server for Biology
|October 10, 2024
Summary
The Arp2/3 complex, regulated by WAVE, is crucial for apical constriction during C. elegans gastrulation. Cell-cell contacts activate WAVE and Arp2/3 basolaterally, driving tissue bending.
Area of Science:
- Cell Biology
- Developmental Biology
- Biochemistry
Background:
- Apical constriction is a fundamental cell shape change essential for tissue bending during embryonic development.
- The precise mechanisms by which localized regulators control actomyosin dynamics during apical constriction are not fully understood.
- The Arp2/3 complex plays a vital role in cytoskeletal organization and has been implicated in various cellular processes, including cell shape changes.
Purpose of the Study:
- To investigate the local regulation of the Arp2/3 complex during apical constriction in C. elegans gastrulation.
- To identify the specific nucleation-promoting factors (NPFs) that regulate Arp2/3 localization and function.
- To elucidate the signaling pathways that control Arp2/3 localization in response to cellular cues.
Main Methods:
- Utilized endogenously-tagged Arp2/3 and NPFs in C. elegans embryos for live imaging.
- Depletion studies using RNA interference (RNAi) to assess the function of specific NPFs.
- Investigated protein localization in response to experimental manipulation of cell-cell contacts.
Main Results:
- Identified WAVE, WASP, and WASH as NPFs that colocalize with Arp2/3 at distinct subcellular locations.
- Demonstrated that depletion of WAVE, but not WASP or WASH, leads to significant gastrulation defects.
- Showed that WAVE and Arp2/3 localize to the basolateral cell cortex at cell-cell contacts, dependent on CED-10/Rac.
- Ectopic cell contacts were sufficient to recruit WAVE and Arp2/3, indicating cell contact as a symmetry-breaking cue.
Conclusions:
- WAVE-mediated regulation of Arp2/3 at basolateral cell-cell contacts is essential for apical constriction during C. elegans gastrulation.
- Cell-cell signaling pathways involving Rac activation are critical for localizing WAVE and Arp2/3 to the basolateral domain.
- These findings highlight the importance of localized Arp2/3 activity at cell-cell junctions for driving tissue morphogenesis.
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