A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29662076.
- Also identified by DOI 10.1038/s41467-018-03571-8 and PMC identifier 5902610.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Chemotaxis
- Class Ia Phosphatidylinositol 3-Kinase
- Epithelial Cells
- Fibroblasts
- rab GTP-Binding Proteins