How do cells sense and respond to adhesive contacts? Diffusion-trapping of laterally mobile membrane proteins at maturing adhesions may initiate signals leading to local cytoskeletal assembly response and lamella formation.
How do cells sense and respond to adhesive contacts? Diffusion-trapping of laterally mobile membrane proteins at maturing adhesions may initiate signals leading to local cytoskeletal assembly response and lamella formation.
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发表时间：
1992-02
影响因子：
4
通讯作者：
David Gingell;Norman F. Owens
中科院分区：
文献类型：
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作者：
David Gingell;Norman F. Owens
关于可扩散分子与受体结合并触发位于质膜上的转导机制的方式，人们已经知道了很多。直到最近，人们才更广泛地认识到这样一个事实，即细胞与它们可以传播的表面之间的接触也可能引发细胞质信号。这包括细胞与细胞之间的接触以及与非细胞表面的粘连。在前一类中，通过T细胞受体复合体的信号转导(Littman，1989)可以通过伺服电机效应激活基于LFA-L/LCAM-1的黏附(Dustin and Springer，1989；van Seventer等人)。1990年；回顾，斯普林格，1990年)。就在最近，Lo等人。(1991)证实中性粒细胞通过E-选择素(ELAM-1)与内皮细胞的黏附产生信号，通过LFA-L/LCAM-1机制增加黏附。赖特等人的重要实验提供了最早明确定义的信号例子之一，该信号是由细胞与底物的黏附启动的。(1983)。他们表明，当巨噬细胞在含有纤维连接蛋白的表面扩散时，#整合素的结合导致信号传播到上层膜，在那里它使两个截然不同的补体受体CR-1(免疫球蛋白超家族)和CR-3(白细胞整合素之一，现在称为Mac-1或CD11b/CD18)内化带有相应配体C3b或iC3b的颗粒。表面受体的数量没有变化。当细胞在缺乏纤维连接蛋白的表面重新铺展时，效果正好相反。Bohnsack等人报道了层粘连蛋白涂层表面的类似结果。(1985年)。通过与底物接触激活血小板也涉及信号传递(Parise，1989；Andrews和Fox，1990)。几乎任何表面，除了血管内皮细胞和某些聚合物(Gingell等人。未发表)可以激活血小板。这种反应包括与第二信使水平的变化和蛋白激酶的激活相关的快速扩散、胞吐和细胞骨架重组，显然受糖蛋白Lib的调节(Ferrell和Martin，1989；Golden等人)。1990年)。局部的信号传递过程也与成纤维细胞识别细胞外基质分子和其他表面有关(Zetter和Brightman，1990)。这涉及到整合素介导的黏附和膜受体与细胞骨架之间连接的组装，导致焦点接触的形成。Massia和Hubbell(1991)最近研究了结合在底物上的RGD多肽的密度与整合素受体聚集之间的关系，从而导致焦点接触的形成。Curtis(1987)认为，黏附，特别是与纤维连接蛋白的黏附，可能会触发细胞激活，Curtis等人的一项创新研究。(1992)强烈暗示整合素介导的信号通路激活了培养的BHK细胞中基于非整合素的黏附机制。
A great deal is known about the ways in which diffusible molecules bind to receptors and trigger transductive mechanisms located in the plasma membrane. Only recently has there been a wider appreciation of the fact that contacts between cells and surfaces on which they can spread may also initiate cytoplasmic signals. This embraces cell-to-cell contact as well as adhesion to noncellular surfaces. In the former category, signal transduction through the T-cell receptor complex (Littman, 1989) can activate adhesion based on LFA-l/lCAM-1 by a servo-motor effect (Dustin and Springer, 1989; van Seventer et al. 1990; review, Springer, 1990). Very recently, Lo et al. (1991) have demonstrated that adhesion of neutrophils to endothelium by means of E selectin (ELAM-1) generates signals responsible for increased adhesion by the LFA-l/lCAM-1 mechanism. One of the first clearly defined examples of a signal initiated by the adhesion of cells to a substratum was provided by the important experiment of Wright et al. (1983). They showed that when macrophages spread on a surface bearing fibronectin, engagement of a # integrin resulted in a signal that spread to the upper membrane where it enabled the two distinctly different complement receptors CR-1 (immunoglobulin superfamily) and CR-3 (one of the leucocyte integrins, now called Mac-1 or CDllb/CD18) to internalize particles bearing the corresponding ligands C3b or iC3b. No change in the number of surface receptors is involved. The effect was reversed on re-spreading the cells on a surface lacking fibronectin. Similar results with a laminin-coated surface were reported by Bohnsack et al. (1985). Blood platelet activation by contact with the substratum also involves signalling (reviews by Parise, 1989; Andrews and Fox, 1990). Almost any surface except vascular endothelium and certain polymers (Gingell et al. unpublished) can activate platelets. The response includes rapid spreading, exocytosis and cytoskeletal reorganization associated with changes in the levels of second messengers and the activation of protein kinases, apparently regulated by glycoprotein lib, Ilia (Ferrell and Martin, 1989; Golden et al. 1990). Localized signalling processes have also been implicated in the recognition of extracellular matrix molecules and other surfaces by fibroblasts (reviewed by Zetter and Brightman, 1990). This involves integrinmediated adhesion and the assembly of linkages between membrane receptors and the cytoskeleton, resulting in the formation of focal contacts. Massia and Hubbell (1991) have recently studied the relationship between the density of RGD peptides bound to a substratum and the clustering of integrin receptors, leading to focal contact formation. Curtis (1987) has argued that adhesion, particularly to fibronectin, may trigger cell activation, and an innovative study by Curtis et al. (1992) has strongly implicated integrin-mediated signalling in the activation of a non-integrin-based adhesion mechanism in cultured BHK cells.