PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex.

Autor: Wang Y; Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France., Chiappetta G; Biological Mass Spectrometry and Proteomics (SMBP), ESPCI Paris, Université PSL, LPC CNRS UMR8249, 75005, Paris, France., Guérois R; Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France., Liu Y; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA., Romero S; Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France., Boesch DJ; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA., Krause M; Randall Centre for Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK., Dessalles CA; LadHyX, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France., Babataheri A; LadHyX, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France., Barakat AI; LadHyX, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France., Chen B; Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA., Vinh J; Biological Mass Spectrometry and Proteomics (SMBP), ESPCI Paris, Université PSL, LPC CNRS UMR8249, 75005, Paris, France., Polesskaya A; Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France. anna.polesskaya@polytechnique.edu., Gautreau AM; Laboratory of Structural Biology of the Cell (BIOC), CNRS UMR7654, École Polytechnique, Institut Polytechnique de Paris, 91120, Palaiseau, France. alexis.gautreau@polytechnique.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jun 15; Vol. 14 (1), pp. 3541. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1038/s41467-023-39276-w
Abstrakt: The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Here, we identify PPP2R1A by proteomics as a protein differentially associated with the WAVE complex subunit ABI1 when RAC1 is activated and downstream generation of branched actin is blocked. PPP2R1A is found to associate at the lamellipodial edge with an alternative form of WAVE complex, the WAVE Shell Complex, that contains NHSL1 instead of the Arp2/3 activating subunit WAVE, as in the canonical WAVE Regulatory Complex. PPP2R1A is required for persistence in random and directed migration assays and for RAC1-dependent actin polymerization in cell extracts. PPP2R1A requirement is abolished by NHSL1 depletion. PPP2R1A mutations found in tumors impair WAVE Shell Complex binding and migration regulation, suggesting that the coupling of PPP2R1A to the WAVE Shell Complex is essential to its function.
(© 2023. The Author(s).)
Databáze: MEDLINE
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