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

Author

Listed:
  • Yanan Wang

    (Institut Polytechnique de Paris)

  • Giovanni Chiappetta

    (Université PSL)

  • Raphaël Guérois

    (Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC))

  • Yijun Liu

    (Iowa State University)

  • Stéphane Romero

    (Institut Polytechnique de Paris)

  • Daniel J. Boesch

    (Iowa State University)

  • Matthias Krause

    (King’s College London)

  • Claire A. Dessalles

    (Institut Polytechnique de Paris)

  • Avin Babataheri

    (Institut Polytechnique de Paris)

  • Abdul I. Barakat

    (Institut Polytechnique de Paris)

  • Baoyu Chen

    (Iowa State University)

  • Joelle Vinh

    (Université PSL)

  • Anna Polesskaya

    (Institut Polytechnique de Paris)

  • Alexis M. Gautreau

    (Institut Polytechnique de Paris)

Abstract

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.

Suggested Citation

  • Yanan Wang & Giovanni Chiappetta & Raphaël Guérois & Yijun Liu & Stéphane Romero & Daniel J. Boesch & Matthias Krause & Claire A. Dessalles & Avin Babataheri & Abdul I. Barakat & Baoyu Chen & Joelle V, 2023. "PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39276-w
    DOI: 10.1038/s41467-023-39276-w
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