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

Corallino Salvatore, 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 Di Fiore, Nils Gauthier, Aldo Ferrari, Paolo Maiuri, Giorgio Scita

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number1475
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Salvatore, C., Malinverno, C., Neumann, B., Tischer, C., Palamidessi, A., Frittoli, E., Panagiotakopoulou, M., Disanza, A., Malet-Engra, G., Nastaly, P., Galli, C., Luise, C., Bertalot, G., Pece, S., Di Fiore, P. P., Gauthier, N., Ferrari, A., Maiuri, P., & Scita, G. (2018). A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration. Nature Communications, 9(1), [1475]. https://doi.org/10.1038/s41467-018-03571-8