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A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration

Author

Listed:
  • Salvatore Corallino

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Chiara Malinverno

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Beate Neumann

    (European Molecular Biology Laboratory)

  • Christian Tischer

    (European Molecular Biology Laboratory)

  • Andrea Palamidessi

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Emanuela Frittoli

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Magdalini Panagiotakopoulou

    (Laboratory of Thermodynamics in Emerging Technologies)

  • Andrea Disanza

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Gema Malet-Engra

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Paulina Nastaly

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Camilla Galli

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Chiara Luise

    (European Institute of Oncology)

  • Giovanni Bertalot

    (European Institute of Oncology)

  • Salvatore Pece

    (European Institute of Oncology)

  • Pier Paolo Fiore

    (IFOM, the FIRC Institute of Molecular Oncology
    European Institute of Oncology
    University of Milan)

  • Nils Gauthier

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Aldo Ferrari

    (Laboratory of Thermodynamics in Emerging Technologies)

  • Paolo Maiuri

    (IFOM, the FIRC Institute of Molecular Oncology)

  • Giorgio Scita

    (IFOM, the FIRC Institute of Molecular Oncology
    University of Milan)

Abstract

How cells move chemotactically remains a major unmet challenge in cell biology. Emerging evidence indicates that for interpreting noisy, shallow gradients of soluble cues a system must behave as an excitable process. Here, through an RNAi-based, high-content screening approach, we identify RAB35 as necessary for the formation of growth factors (GFs)-induced waves of circular dorsal ruffles (CDRs), apically restricted actin-rich migratory protrusions. RAB35 is sufficient to induce recurrent and polarized CDRs that travel as propagating waves, thus behaving as an excitable system that can be biased to control cell steering. Consistently, RAB35 is essential for promoting directed chemotactic migration and chemoinvasion of various cells in response to gradients of motogenic GFs. Molecularly, RAB35 does so by directly regulating the activity of p85/PI3K polarity axis. We propose that RAB35 is a molecular determinant for the control of an excitable, oscillatory system that acts as a steering wheel for GF-mediated chemotaxis and chemoinvasion.

Suggested Citation

  • Salvatore Corallino & Chiara Malinverno & Beate Neumann & Christian Tischer & Andrea Palamidessi & Emanuela Frittoli & Magdalini Panagiotakopoulou & Andrea Disanza & Gema Malet-Engra & Paulina Nastaly, 2018. "A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03571-8
    DOI: 10.1038/s41467-018-03571-8
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