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

Fingerprint

Self assembly
Actins
Neutrophils
Chemotactic Factors
Myosin Type II
rho-Associated Kinases
rho GTP-Binding Proteins
Pseudopodia
Monomeric GTP-Binding Proteins
HL-60 Cells
Mutant Proteins
Myosins
GTP-Binding Proteins
Leukocytes
Chemical activation
Pharmacology
Lipids
Experiments

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Xu, J., Wang, F., Van Keymeulen, A., Herzmark, P., Straight, A., Kelly, K., ... 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

Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. / Xu, Jingsong; Wang, Fei; Van Keymeulen, Alexandra; Herzmark, Paul; Straight, Aaron; Kelly, Kathleen; Takuwa, Yoh; Sugimoto, Naotoshi; Mitchison, Timothy; Bourne, Henry R.

In: Cell, Vol. 114, No. 2, 25.07.2003, p. 201-214.

Research output: Contribution to journalArticle

Xu, J, Wang, F, Van Keymeulen, A, Herzmark, P, Straight, A, Kelly, K, Takuwa, Y, Sugimoto, N, Mitchison, T & Bourne, HR 2003, 'Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils', Cell, vol. 114, no. 2, pp. 201-214. https://doi.org/10.1016/S0092-8674(03)00555-5
Xu J, Wang F, Van Keymeulen A, Herzmark P, Straight A, Kelly K et al. Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. Cell. 2003 Jul 25;114(2):201-214. https://doi.org/10.1016/S0092-8674(03)00555-5
Xu, Jingsong ; Wang, Fei ; Van Keymeulen, Alexandra ; Herzmark, Paul ; Straight, Aaron ; Kelly, Kathleen ; Takuwa, Yoh ; Sugimoto, Naotoshi ; Mitchison, Timothy ; Bourne, Henry R. / Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils. In: Cell. 2003 ; Vol. 114, No. 2. pp. 201-214.
@article{3430147d48694313989293a30bbb5cd9,
title = "Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils",
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.",
author = "Jingsong Xu and Fei Wang and {Van Keymeulen}, Alexandra and Paul Herzmark and Aaron Straight and Kathleen Kelly and Yoh Takuwa and Naotoshi Sugimoto and Timothy Mitchison and Bourne, {Henry R.}",
year = "2003",
month = "7",
day = "25",
doi = "10.1016/S0092-8674(03)00555-5",
language = "English (US)",
volume = "114",
pages = "201--214",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Divergent signals and cytoskeletal assemblies regulate self-organizing polarity in neutrophils

AU - Xu, Jingsong

AU - Wang, Fei

AU - Van Keymeulen, Alexandra

AU - Herzmark, Paul

AU - Straight, Aaron

AU - Kelly, Kathleen

AU - Takuwa, Yoh

AU - Sugimoto, Naotoshi

AU - Mitchison, Timothy

AU - Bourne, Henry R.

PY - 2003/7/25

Y1 - 2003/7/25

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0042354714&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042354714&partnerID=8YFLogxK

U2 - 10.1016/S0092-8674(03)00555-5

DO - 10.1016/S0092-8674(03)00555-5

M3 - Article

C2 - 12887922

AN - SCOPUS:0042354714

VL - 114

SP - 201

EP - 214

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -