• Citer

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

par Xu, J.;Wang, F.;Van Keymeulen, Alexandra ;Herzmark, Paul;Straight, Aaron;Kelly, Kathleen;Takuwa, Yoh;Sugimoto, Naotoshi;Mitchison, Timothy;Bourne, Henry R
Référence Cell, 114, 2, page (201-214)
Publication Publié, 2003-07

Article révisé par les pairs

• Détails
• Contenu

Résumé :

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.