Lidke Diane S, Lidke Keith A, Rieger Bernd, Jovin Thomas M, Arndt-Jovin Donna J
Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077, Goettingen, Germany.
J Cell Biol. 2005 Aug 15;170(4):619-26. doi: 10.1083/jcb.200503140.
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.
位于细胞丝状伪足上的表皮生长因子受体（ErbB1）在结合表皮生长因子（EGF）并激活受体酪氨酸激酶后会经历系统性的逆行运输。ErbB1受体酪氨酸激酶的特异性抑制剂以及肌动蛋白细胞骨架破坏剂细胞松弛素D，会消除受体-配体复合物的运输，但不会消除其自由扩散。通过追踪与荧光量子点偶联的EGF标记的受体，以单分子灵敏度测定了扩散常数和运输速率。逆行运输先于受体胞吞作用，后者发生在丝状伪足的基部。运输的启动需要至少两个配体化受体的相互作用和协同激活，并以与肌动蛋白结合介导的恒定速率进行。这些发现提示了一种机制，通过该机制丝状伪足能够检测远离细胞体的效应分子的存在和浓度，并通过激活受体的定向运输介导细胞反应。
