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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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    1. Ah-Lai Law & Shamsinar Jalal & Tommy Pallett & Fuad Mosis & Ahmad Guni & Simon Brayford & Lawrence Yolland & Stefania Marcotti & James A. Levitt & Simon P. Poland & Maia Rowe-Sampson & Anett Jandke & , 2021. "Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    2. Bojian Ding & Sheng Yang & Matthias Schaks & Yijun Liu & Abbigale J. Brown & Klemens Rottner & Saikat Chowdhury & Baoyu Chen, 2022. "Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    4. Zhucheng Chen & Dominika Borek & Shae B. Padrick & Timothy S. Gomez & Zoltan Metlagel & Ayman M. Ismail & Junko Umetani & Daniel D. Billadeau & Zbyszek Otwinowski & Michael K. Rosen, 2010. "Structure and control of the actin regulatory WAVE complex," Nature, Nature, vol. 468(7323), pages 533-538, November.
    5. Douglas A. Levine, 2013. "Integrated genomic characterization of endometrial carcinoma," Nature, Nature, vol. 497(7447), pages 67-73, May.
    6. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    7. Fred E. Fregoso & Trevor Eeuwen & Gleb Simanov & Grzegorz Rebowski & Malgorzata Boczkowska & Austin Zimmet & Alexis M. Gautreau & Roberto Dominguez, 2022. "Molecular mechanism of Arp2/3 complex inhibition by Arpin," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Irene Dang & Roman Gorelik & Carla Sousa-Blin & Emmanuel Derivery & Christophe Guérin & Joern Linkner & Maria Nemethova & Julien G. Dumortier & Florence A. Giger & Tamara A. Chipysheva & Valeria D. Er, 2013. "Inhibitory signalling to the Arp2/3 complex steers cell migration," Nature, Nature, vol. 503(7475), pages 281-284, November.
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