Locally excitable Cdc42 signals steer cells during chemotaxis

Hee Won Yang, Sean Collins, Tobias Meyer

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Neutrophils and other amoeboid cells chemotax by steering their front ends towards chemoattractant. Although Ras, Rac, Cdc42 and RhoA small GTPases all regulate chemotaxis, it has been unclear how they spatiotemporally control polarization and steering. Using fluorescence biosensors in neutrophil-like PLB-985 cells and photorelease of chemoattractant, we show that local Cdc42 signals, but not those of Rac, RhoA or Ras, precede cell turning during chemotaxis. Furthermore, pre-existing local Cdc42 signals in morphologically unpolarized cells predict the future direction of movement on uniform stimulation. Moreover, inhibition of actin polymerization uncovers recurring local Cdc42 activity pulses, suggesting that Cdc42 has the excitable characteristic of the compass activity proposed in models of chemotaxis. Globally, Cdc42 antagonizes RhoA, and maintains a steep spatial activity gradient during migration, whereas Ras and Rac form shallow gradients. Thus, chemotactic steering and de novo polarization are both directed by locally excitable Cdc42 signals.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalNature Cell Biology
Volume18
Issue number2
DOIs
StatePublished - Jan 28 2016

ASJC Scopus subject areas

  • Cell Biology

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