A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration
Salvatore Corallino,
Chiara Malinverno,
Beate Neumann,
Christian Tischer,
Andrea Palamidessi,
Emanuela Frittoli,
Magdalini Panagiotakopoulou,
Andrea Disanza,
Gema Malet-Engra,
Paulina Nastaly,
Camilla Galli,
Chiara Luise,
Giovanni Bertalot,
Salvatore Pece,
Pier Paolo Fiore,
Nils Gauthier,
Aldo Ferrari,
Paolo Maiuri and
Giorgio Scita ()
Additional contact information
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
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
Nature Communications, 2018, vol. 9, issue 1, 1-19
Abstract:
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.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03571-8
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DOI: 10.1038/s41467-018-03571-8
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