Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors.
Reaching out for signals: filopodia sense EGF and respond by directed retrograde transport of activated receptors.
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DOI：
10.1083/jcb.200503140
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发表时间：
2005-08-15
期刊：
影响因子：
--
通讯作者：
Arndt-Jovin DJ
中科院分区：
文献类型：
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作者：
Lidke DS;Lidke KA;Rieger B;Jovin TM;Arndt-Jovin DJ
位于细胞丝状伪足上的ErbB 1受体在与表皮生长因子（EGF）结合并激活受体酪氨酸激酶后进行系统性逆行转运。erbB 1受体酪氨酸激酶的特异性抑制剂以及细胞松弛素D（一种肌动蛋白细胞骨架的破坏剂）可消除受体-配体复合物的转运，但不能消除其自由扩散。扩散常数和运输速率测定与单分子灵敏度跟踪受体标记的EGF共轭荧光量子点。逆行运输先于受体内吞作用，发生在丝状伪足的基部。转运的启动需要至少两个配体受体的相互作用和协同激活，并通过与肌动蛋白的结合以恒定的速率进行。这些发现表明丝状伪足检测远离细胞体的效应分子的存在和浓度并通过活化受体的定向运输介导细胞反应的机制。
ErbB1 receptors situated on cellular filopodia undergo systematic retrograde transport after binding of the epidermal growth factor (EGF) and activation of the receptor tyrosine kinase. Specific inhibitors of the erbB1 receptor tyrosine kinase as well as cytochalasin D, a disruptor of the actin cytoskeleton, abolish transport but not free diffusion of the receptor–ligand complex. Diffusion constants and transport rates were determined with single molecule sensitivity by tracking receptors labeled with EGF conjugated to fluorescent quantum dots. Retrograde transport precedes receptor endocytosis, which occurs at the base of the filopodia. Initiation of transport requires the interaction and concerted activation of at least two liganded receptors and proceeds at a constant rate mediated by association with actin. These findings suggest a mechanism by which filopodia detect the presence and concentration of effector molecules far from the cell body and mediate cellular responses via directed transport of activated receptors.