Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils

Jingsong Xu, Fei Wang, Alexandra Van Keymeulen, Paul Herzmark, Aaron Straight, Kathleen Kelly, Yoh Takuwa, Naotoshi Sugimoto, Timothy Mitchison, Henry R. Bourne

Research output: Contribution to journalArticle

Abstract

Like neutrophilic leukocytes, differentiated HL-60 cells respond to chemoattractant by adopting a polarized morphology, with F-actin in a protruding pseudopod at the leading edge and contractile actin-myosin complexes at the back and sides. Experiments with pharmacological inhibitors, toxins, and mutant proteins show that this polarity depends on divergent, opposing "frontness" and "backness" signals generated by different receptor-activated trimeric G proteins. Frontness depends upon Gi-mediated production of 3′-phosphoinositol lipids (PI3Ps), the activated form of Rac, a small GTPase, and F-actin. G12 and G13 trigger backness signals, including activation of a second GTPase (Rho), a Rho-dependent kinase, and myosin II. Functional incompatibility causes the two resulting actin assemblies to aggregate into separate domains, making the leading edge more sensitive to attractant than the back. The latter effect explains both the neutrophil's ability to polarize in uniform concentrations of chemoattractant and its response to reversal of an attractant gradient by performing a U-turn.

Original languageEnglish (US)
Pages (from-to)201-214
Number of pages14
JournalCell
Volume114
Issue number2
DOIs
StatePublished - Jul 25 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K., Takuwa, Y., Sugimoto, N., Mitchison, T., & Bourne, H. R. (2003). Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell, 114(2), 201-214. https://doi.org/10.1016/S0092-8674(03)00555-5