Journal article
Myosin II and Arp2/3 cross-talk governs intracellular hydraulic pressure and lamellipodia formation
Molecular biology of the cell, v 32(7), pp 579-589
01 Apr 2021
PMID: 33502904
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Human fibroblasts can switch between lamellipodia-dependent and -independent migration mechanisms on two-dimensional surfaces and in three-dimensional (3D) matrices. RhoA GTPase activity governs the switch from low-pressure lamellipodia to high-pressure lobopodia in response to the physical structure of the 3D matrix. Inhibiting actomyosin contractility in these cells reduces intracellular pressure and reverts lobopodia to lamellipodial protrusions via an unknown mechanism. To test the hypothesis that high pressure physically prevents lamellipodia formation, we manipulated pressure by activating RhoA or changing the osmolarity of the extracellular environment and imaged cell protrusions. We find RhoA activity inhibits Racl -mediated lamellipodia formation through two distinct pathways. First, RhoA boosts intracellular pressure by increasing actomyosin contractility and water influx but acts upstream of Racl to inhibit lamellipodia formation. Increasing osmotic pressure revealed a second RhoA pathway, which acts through nonmuscle myosin II (NMII) to disrupt lamellipodia downstream from Rac1 and elevate pressure. Interestingly, Arp2/3 inhibition triggered a NMII-dependent increase in intracellular pressure, along with lamellipodia disruption. Together, these results suggest that actomyosin contractility and water influx are coordinated to increase intracellular pressure, and RhoA signaling can inhibit lamellipodia formation via two distinct pathways in high-pressure cells.
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Details
- Title
- Myosin II and Arp2/3 cross-talk governs intracellular hydraulic pressure and lamellipodia formation
- Creators
- Shivani Patel - Drexel UniversityDonna McKeon - Drexel UniversityKimheak Sao - Drexel UniversityChangsong Yang - University of PennsylvaniaNicole M. Naranjo - Drexel UniversityTatyana M. Svitkina - University of PennsylvaniaRyan J. Petrie - Drexel University
- Publication Details
- Molecular biology of the cell, v 32(7), pp 579-589
- Publisher
- Amer Soc Cell Biology
- Number of pages
- 11
- Grant note
- R01GM126054; R01GM095977 / National Institute of General Medical Sciences of the National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000636666900007
- Scopus ID
- 2-s2.0-85103802333
- Other Identifier
- 991019167785604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology