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Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration

Author

Listed:
  • Ah-Lai Law

    (King’s College London
    School of Life Sciences, University of Bedfordshire)

  • Shamsinar Jalal

    (King’s College London)

  • Tommy Pallett

    (King’s College London)

  • Fuad Mosis

    (King’s College London)

  • Ahmad Guni

    (King’s College London)

  • Simon Brayford

    (King’s College London)

  • Lawrence Yolland

    (King’s College London)

  • Stefania Marcotti

    (King’s College London)

  • James A. Levitt

    (King’s College London)

  • Simon P. Poland

    (King’s College London)

  • Maia Rowe-Sampson

    (King’s College London
    King’s College London)

  • Anett Jandke

    (King’s College London
    The Francis Crick Institute)

  • Robert Köchl

    (King’s College London)

  • Giordano Pula

    (King’s College London
    Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg (UKE))

  • Simon M. Ameer-Beg

    (King’s College London)

  • Brian Marc Stramer

    (King’s College London)

  • Matthias Krause

    (King’s College London)

Abstract

Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin density of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25916-6
    DOI: 10.1038/s41467-021-25916-6
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    Cited by:

    1. 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.

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