Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis

Susan Lee, Zhouxin Shen, Douglas Robinson, Steven Briggs, Richard A. Firtel

Research output: Contribution to journalArticle

Abstract

In response to directional stimulation by a chemoattractant, cells rapidly activate a series of signaling pathways at the site closest to the chemoattractant source that leads to F-actin polymerization, pseudopod formation, and directional movement up the gradient. Ras proteins are major regulators of chemotaxis in Dictyostelium; they are activated at the leading edge, are required for chemoattractant-mediated activation of PI3K and TORC2, and are one of the most rapid responders, with activity peaking at ∼3 s after stimulation. We demonstrate that in myosin II (MyoII) null cells, Ras activation is highly extended and is not restricted to the site closest to the chemoattractant source. This causes elevated, extended, and spatially misregulated activation of PI3K and TORC2 and their effectors Akt/PKB and PKBR1, as well as elevated F-actin polymerization. We further demonstrate that disruption of specific IQGAP/cortexillin complexes, which also regulate cortical mechanics, causes extended activation of PI3K and Akt/PKB but not Ras activation. Our findings suggest that MyoII and IQGAP/cortexillin play key roles in spatially and temporally regulating leading-edge activity and, through this, the ability of cells to restrict the site of pseudopod formation.

Original languageEnglish (US)
Pages (from-to)1810-1824
Number of pages15
JournalMolecular Biology of the Cell
Volume21
Issue number11
DOIs
StatePublished - Jun 1 2010

Fingerprint

Chemotactic Factors
Chemotaxis
Cytoskeleton
Phosphatidylinositol 3-Kinases
Myosin Type II
Pseudopodia
Polymerization
Actins
ras Proteins
Null Lymphocytes
Aptitude
Dictyostelium
Mechanics
TOR complex 2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

Cite this

Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis. / Lee, Susan; Shen, Zhouxin; Robinson, Douglas; Briggs, Steven; Firtel, Richard A.

In: Molecular Biology of the Cell, Vol. 21, No. 11, 01.06.2010, p. 1810-1824.

Research output: Contribution to journalArticle

Lee, Susan ; Shen, Zhouxin ; Robinson, Douglas ; Briggs, Steven ; Firtel, Richard A. / Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis. In: Molecular Biology of the Cell. 2010 ; Vol. 21, No. 11. pp. 1810-1824.
@article{645e9aced8f14bd49bdbe9ade12bbb79,
title = "Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis",
abstract = "In response to directional stimulation by a chemoattractant, cells rapidly activate a series of signaling pathways at the site closest to the chemoattractant source that leads to F-actin polymerization, pseudopod formation, and directional movement up the gradient. Ras proteins are major regulators of chemotaxis in Dictyostelium; they are activated at the leading edge, are required for chemoattractant-mediated activation of PI3K and TORC2, and are one of the most rapid responders, with activity peaking at ∼3 s after stimulation. We demonstrate that in myosin II (MyoII) null cells, Ras activation is highly extended and is not restricted to the site closest to the chemoattractant source. This causes elevated, extended, and spatially misregulated activation of PI3K and TORC2 and their effectors Akt/PKB and PKBR1, as well as elevated F-actin polymerization. We further demonstrate that disruption of specific IQGAP/cortexillin complexes, which also regulate cortical mechanics, causes extended activation of PI3K and Akt/PKB but not Ras activation. Our findings suggest that MyoII and IQGAP/cortexillin play key roles in spatially and temporally regulating leading-edge activity and, through this, the ability of cells to restrict the site of pseudopod formation.",
author = "Susan Lee and Zhouxin Shen and Douglas Robinson and Steven Briggs and Firtel, {Richard A.}",
year = "2010",
month = "6",
day = "1",
doi = "10.1091/mbc.E10-01-0009",
language = "English (US)",
volume = "21",
pages = "1810--1824",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "11",

}

TY - JOUR

T1 - Involvement of the cytoskeleton in controlling leading-edge function during chemotaxis

AU - Lee, Susan

AU - Shen, Zhouxin

AU - Robinson, Douglas

AU - Briggs, Steven

AU - Firtel, Richard A.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - In response to directional stimulation by a chemoattractant, cells rapidly activate a series of signaling pathways at the site closest to the chemoattractant source that leads to F-actin polymerization, pseudopod formation, and directional movement up the gradient. Ras proteins are major regulators of chemotaxis in Dictyostelium; they are activated at the leading edge, are required for chemoattractant-mediated activation of PI3K and TORC2, and are one of the most rapid responders, with activity peaking at ∼3 s after stimulation. We demonstrate that in myosin II (MyoII) null cells, Ras activation is highly extended and is not restricted to the site closest to the chemoattractant source. This causes elevated, extended, and spatially misregulated activation of PI3K and TORC2 and their effectors Akt/PKB and PKBR1, as well as elevated F-actin polymerization. We further demonstrate that disruption of specific IQGAP/cortexillin complexes, which also regulate cortical mechanics, causes extended activation of PI3K and Akt/PKB but not Ras activation. Our findings suggest that MyoII and IQGAP/cortexillin play key roles in spatially and temporally regulating leading-edge activity and, through this, the ability of cells to restrict the site of pseudopod formation.

AB - In response to directional stimulation by a chemoattractant, cells rapidly activate a series of signaling pathways at the site closest to the chemoattractant source that leads to F-actin polymerization, pseudopod formation, and directional movement up the gradient. Ras proteins are major regulators of chemotaxis in Dictyostelium; they are activated at the leading edge, are required for chemoattractant-mediated activation of PI3K and TORC2, and are one of the most rapid responders, with activity peaking at ∼3 s after stimulation. We demonstrate that in myosin II (MyoII) null cells, Ras activation is highly extended and is not restricted to the site closest to the chemoattractant source. This causes elevated, extended, and spatially misregulated activation of PI3K and TORC2 and their effectors Akt/PKB and PKBR1, as well as elevated F-actin polymerization. We further demonstrate that disruption of specific IQGAP/cortexillin complexes, which also regulate cortical mechanics, causes extended activation of PI3K and Akt/PKB but not Ras activation. Our findings suggest that MyoII and IQGAP/cortexillin play key roles in spatially and temporally regulating leading-edge activity and, through this, the ability of cells to restrict the site of pseudopod formation.

UR - http://www.scopus.com/inward/record.url?scp=77952925797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952925797&partnerID=8YFLogxK

U2 - 10.1091/mbc.E10-01-0009

DO - 10.1091/mbc.E10-01-0009

M3 - Article

C2 - 20375144

AN - SCOPUS:77952925797

VL - 21

SP - 1810

EP - 1824

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 11

ER -