Are Filopodia Privileged Signaling Structures in Migrating Cells?
Are Filopodia Privileged Signaling Structures in Migrating Cells?
复制标题
丝状伪足在迁移细胞中是否具有特权信号结构？
DOI：
10.1016/j.bpj.2016.09.022
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发表时间：
2016
影响因子：
3.4
通讯作者：
Haugh,JasonM
中科院分区：
文献类型：
--
作者：
Johnson,HeathE;Haugh,JasonM
丝状伪足是指状细结构，含有成束的肌动蛋白丝，从细胞周边突出。这些结构被武断地赋予了在微环境中感知线索的能力，这意味着丝状伪足促进了局部信号转导，但它们的小直径阻碍了其中动态过程的成像。为了克服这一挑战，我们分析了共表达质膜标记物或标记的AktPH结构域的迁移成纤维细胞的全内反射荧光图像，AktPH结构域是一种通过磷酸肌醇3-激酶途径进行信号传导的易位生物传感器，沿着细胞溶质体积标记物。我们设计了一个计划，估计使用膜标记或体积标记数据的丝状伪足的半径，我们使用该信息来解释生物传感器数据中的几何效应。保守估计的相对目标分子丰度，它揭示了丝状伪足通常具有较高的密度比相邻区域的细胞周边的3′磷酸肌醇。至少在这种情况下，该分析支持了丝状伪足信号假说。
Filopodia are thin, fingerlike structures that contain bundled actin filaments and project from the cell periphery. These structures are dogmatically endowed with the ability to sense cues in the microenvironment, implying that filopodia foster local signal transduction, yet their small diameter hampers the imaging of dynamic processes therein. To overcome this challenge, we analyzed total internal reflection fluorescence images of migrating fibroblasts coexpressing either a plasma membrane marker or tagged AktPH domain, a translocation biosensor for signaling through the phosphoinositide 3-kinase pathway, along with a cytosolic volume marker. We devised a scheme to estimate the radii of filopodia using either the membrane marker or volume marker data, and we used that information to account for geometry effects in the biosensor data. With conservative estimates of relative target molecule abundance, it is revealed that filopodia typically harbor higher densities of 3′ phosphoinositides than adjacent regions at the cell periphery. In this context at least, the analysis supports the filopodial signaling hypothesis.