TY - JOUR
T1 - Membrane lipid organization is critical for human neutrophil polarization
AU - Pierini, Lynda M.
AU - Eddy, Robert J.
AU - Fuortes, Michele
AU - Seveau, Stéphanie
AU - Casulo, Carlo
AU - Maxfield, Frederick R.
PY - 2003/3/21
Y1 - 2003/3/21
N2 - In response to chemoattractants neutrophils extend an actin-rich pseudopod, which imparts morphological polarity and is required for migration. Even when stimulated by an isotropic bath of chemoattractant, neutrophils exhibit persistent polarization and continued lamellipod formation at the front, suggesting that the cells establish an internal polarity. In this report, we show that perturbing lipid organization by depleting plasma membrane cholesterol levels reversibly inhibits cell polarization and migration. Among other receptor-mediated responses, β2 integrin up-regulation was unaffected, and initial calcium mobilization was only partially reduced by cholesterol depletion, indicating that this treatment did not abrogate initial receptor-mediated signal transduction. Interestingly, cholesterol depletion did not prevent initial activation of the GTPase Rac or an initial burst of actin polymerization, but rather it inhibited prolonged activation of Rac and sustained actin polymerization. Collectively, these findings support a model in which the plasma membrane is organized into domains that aid in amplifying the chemoattractant gradient and maintaining cell polarization.
AB - In response to chemoattractants neutrophils extend an actin-rich pseudopod, which imparts morphological polarity and is required for migration. Even when stimulated by an isotropic bath of chemoattractant, neutrophils exhibit persistent polarization and continued lamellipod formation at the front, suggesting that the cells establish an internal polarity. In this report, we show that perturbing lipid organization by depleting plasma membrane cholesterol levels reversibly inhibits cell polarization and migration. Among other receptor-mediated responses, β2 integrin up-regulation was unaffected, and initial calcium mobilization was only partially reduced by cholesterol depletion, indicating that this treatment did not abrogate initial receptor-mediated signal transduction. Interestingly, cholesterol depletion did not prevent initial activation of the GTPase Rac or an initial burst of actin polymerization, but rather it inhibited prolonged activation of Rac and sustained actin polymerization. Collectively, these findings support a model in which the plasma membrane is organized into domains that aid in amplifying the chemoattractant gradient and maintaining cell polarization.
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U2 - 10.1074/jbc.M212386200
DO - 10.1074/jbc.M212386200
M3 - Article
C2 - 12522144
AN - SCOPUS:0037562005
SN - 0021-9258
VL - 278
SP - 10831
EP - 10841
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -