Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis.
Dynamic redistribution of raft domains as an organizing platform for signaling during cell chemotaxis.
复制标题
筏结构域的动态重新分布是细胞趋化过程中信号传导的组织平台。
DOI：
10.1083/jcb.200309101
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发表时间：
2004-03-01
影响因子：
7.8
通讯作者：
Mañes, S
中科院分区：
文献类型：
--
作者：
Gómez-Moutón, C;Lacalle, RA;Mira, E;Jiménez-Baranda, S;Barber, DF;Carrera, AC;Martínez, C;Mañes, S
信号分子的空间限制性激活控制着细胞迁移的关键方面;然而，实现这一点的机制仍然未知。使用延时共聚焦显微镜，我们分析了在化学引诱剂刺激的表达糖基磷脂酰肌醇锚定的绿色荧光蛋白（GFP-GPI）的白细胞中脂筏的动态再分布。化学引诱剂诱导持久的GFP-GPI再分配的前沿筏（L筏）和尾足动物筏Jurkat，HL 60，和二甲基亚砜分化HL 60细胞在百日咳毒素敏感，肌动蛋白依赖的方式。一个跨膜，非筏GFP蛋白均匀分布在移动的细胞。GFP-CCR 5嵌合体在L筏中分配，在前缘积累，并且CCR 5重新分布与极化运动细胞中L筏中磷脂酰肌醇-3激酶γ的募集和激活一致。膜胆固醇耗竭阻碍筏再分配和不对称的招聘PI 3 K的细胞侧面对的化学引诱物源。这是第一个直接的证据表明，脂筏秩序的空间信号在移动的哺乳动物细胞，通过集中在前沿的梯度传感机制。
Spatially restricted activation of signaling molecules governs critical aspects of cell migration; the mechanism by which this is achieved nonetheless remains unknown. Using time-lapse confocal microscopy, we analyzed dynamic redistribution of lipid rafts in chemoattractant-stimulated leukocytes expressing glycosyl phosphatidylinositol–anchored green fluorescent protein (GFP-GPI). Chemoattractants induced persistent GFP-GPI redistribution to the leading edge raft (L raft) and uropod rafts of Jurkat, HL60, and dimethyl sulfoxide–differentiated HL60 cells in a pertussis toxin–sensitive, actin-dependent manner. A transmembrane, nonraft GFP protein was distributed homogeneously in moving cells. A GFP-CCR5 chimera, which partitions in L rafts, accumulated at the leading edge, and CCR5 redistribution coincided with recruitment and activation of phosphatidylinositol-3 kinase γ in L rafts in polarized, moving cells. Membrane cholesterol depletion impeded raft redistribution and asymmetric recruitment of PI3K to the cell side facing the chemoattractant source. This is the first direct evidence that lipid rafts order spatial signaling in moving mammalian cells, by concentrating the gradient sensing machinery at the leading edge.
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影响因子：
7.8
作者：
Pralle, A;Keller, P;Florin, E L;Simons, K;Horber, J K
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