Polarity and Gradient Sensing are Independent of Cell Movement and Cytoskeletal Dynam-ics

【作者】 王铭洁； 蔡文杰； Peter N.Devreotes；

【Author】 Peter N.Devreotes;

【机构】 复旦大学上海医学院生理与病理生理学系； 美国霍普金斯大学医学院细胞生物学系； 上海理工大学基础医学系；

【摘要】 Migrating cells display signal transduction events such as activation of PI3K and Scar/Wave and respond more readily to chemotactic stimuli at the leading edge.Inhibiting actin polymerization leads to uniform sensitivity.However,when human neutrophils were"stalled"by simultaneously blocking actin and myosin dynamics,they maintained the gradient of responsiveness to chemoattractant and also displayednoise-driven PIP3 flashes on the basal membrane,localized toward the front.Thus,polarized sensitivity does not require migration or cytoskeletal dynamics.The threshold for response is correlated with the static F-actin distribution but not cell shape or volume changes,membrane fluidity,or the pre-existing distribution of PI3K.The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model but the overall direction of the response was biased by the internal axis of polarity,suggesting that gradient sensing and polarity are separable phenomena that sum vectorially.更多还原

【Abstract】 Migrating cells display signal transduction events such as activation of PI3 K and Scar/Wave and respond more readily to chemotactic stimuli at the leading edge.Inhibiting actin polymerization leads to uniform sensitivity.However,when human neutrophils were "stalled" by simultaneously blocking actin and myosin dynamics,they maintained the gradient of responsiveness to chemoattractant and also displayednoise-driven PIP3 flashes on the basal membrane,localized toward the front.Thus,polarized sensitivity does not require migration or cytoskeletal dynamics.The threshold for response is correlated with the static F-actin distribution but not cell shape or volume changes,membrane fluidity,or the pre-existing distribution of PI3 K.The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model but the overall direction of the response was biased by the internal axis of polarity,suggesting that gradient sensing and polarity are separable phenomena that sum vectorially.更多还原