期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 87, 期 4, 页码 545-555出版社
WILEY
DOI: 10.1189/jlb.0609390
关键词
neutrophils; phagocytosis; chemotaxis
资金
- CIHR
In this investigation, we used primary murine neutrophils to demonstrate that local changes in membrane phospholipid composition alter the net cytoplasmic membrane surface charge, which results in selective recruitment of Rac1 or Rac2 based on the net charge of their respective C-terminal domains. Murine neutrophils undergoing chemotaxis or carrying out phagocytosis were transfected with K-ras4B-derived membrane charge biosensors and lipid markers, which allowed us to simultaneously monitor the levels of PIP2, PIP3, and PS and net membrane charge of the newly developing phagosome membrane and plasma membrane. Our results indicate that the combination of PIP2, PIP3, and PS generates a high negative charge (-8) at the plasma membrane of actin-rich pseudopods, where active Rac1 preferentially localizes during phagosome formation. The lipid metabolism that occurs during phagosome maturation results in the localized depletion of PIP2, PIP3, and partial decrease in PS. This creates a moderately negative net charge that correlates with the localization of active Rac2. Conversely, the accumulation of PIP3 at the leading-edge membrane during chemotaxis generates a polarized accumulation of negative charges that recruits Rac1. These results provide evidence that alterations in membrane lipid composition and inner-membrane surface charge are important elements for the recruitment of differentially charged proteins and localization of signaling pathways during phagocytosis and chemotaxis in neutrophils. J. Leukoc. Biol. 87: 545-555; 2010.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据