Murphy-Ullrich J E
Department of Pathology, University of Alabama at Birmingham, G038 Volker Hall, 1670 University Boulevard, Birmingham, Alabama 35294-0019, USA.
J Clin Invest. 2001 Apr;107(7):785-90. doi: 10.1172/JCI12609.
The process of cellular de-adhesion is potentially important for the ability of a cell to participate in morphogenesis and to respond to injurious stimuli. Cellular de-adhesion is induced by the highly regulated matricellular proteins TSP1 and 2, tenascin-C, and SPARC. These proteins induce a rapid transition to an intermediate state of adhesiveness characterized by loss of actin-containing stress fibers and restructuring of the focal adhesion plaque that includes loss of vinculin and alpha-actinin, but not of talin or integrin. This process involves intracellular signaling mediators, which are engaged in response to matrix protein-receptor interactions. Each of these proteins employs different receptors and signaling pathways to achieve this common morphologic endpoint. What is the function of this intermediate adhesive state and what is the physiologic significance of this action of the matricellular proteins? Given that matricellular proteins are expressed in response to injury and during development, one can speculate that the intermediate adhesive state is an adaptive condition that facilitates expression of specific genes that are involved in repair and adaptation. Since cell shape is maintained in weakly adherent cells, this state might induce survival signals to prevent apoptosis due to loss of strong cell adhesion, but yet allow for cell locomotion. The three matricellular proteins considered here might each preferentially facilitate one or more aspects of this adaptive response rather than all of these equally. Currently, we have only preliminary data to support the specific ideas proposed in this article. It will be interesting in the next several years to continue to elucidate the biological roles of the intermediate adhesive state induced by these matricellular proteins. and focal adhesions in a cell that nevertheless maintains a spread, extended morphology and integrin clustering. TSP1, tenascin-C, and SPARC induce the intermediate adhesive state, as shown by the red arrows. The significance of each adhesive state for cell behavior is indicated beneath the cells. The weak adhesive state would be consistent with cells undergoing apoptosis during remodeling or those undergoing cytokinesis. The strong adhesive state is characteristic of a differentiated, quiescent cell, whereas cells in the intermediate adhesive state would include those involved in responding to injury during wound healing or in tissue remodeling during morphogenesis.
细胞去黏附过程对于细胞参与形态发生及应对损伤刺激的能力可能具有重要意义。细胞去黏附由高度调控的基质细胞蛋白血小板反应蛋白1和2、腱生蛋白-C以及富含半胱氨酸的酸性分泌蛋白诱导产生。这些蛋白诱导细胞迅速转变为一种中间黏附状态，其特征为含肌动蛋白的应力纤维丧失以及黏着斑重塑，包括纽蛋白和α-辅肌动蛋白丧失，但踝蛋白或整合素未丧失。此过程涉及细胞内信号转导介质，它们会响应基质蛋白-受体相互作用而被激活。这些蛋白中的每一种都利用不同的受体和信号通路来达成这一共同的形态学终点。这种中间黏附状态的功能是什么，基质细胞蛋白的这一作用又有何生理意义？鉴于基质细胞蛋白在损伤应答及发育过程中表达，人们可以推测中间黏附状态是一种适应性状态，有助于表达参与修复和适应的特定基因。由于在弱黏附细胞中细胞形状得以维持，这种状态可能会诱导存活信号以防止因强细胞黏附丧失而导致的细胞凋亡，但同时又允许细胞移动。这里所考虑的三种基质细胞蛋白可能各自优先促进这种适应性反应的一个或多个方面，而非同等地促进所有方面。目前，我们仅有初步数据来支持本文所提出的具体观点。在接下来的几年里，继续阐明这些基质细胞蛋白所诱导的中间黏附状态以及黏着斑在仍保持铺展、伸展形态及整合素聚集的细胞中的生物学作用将会很有趣。血小板反应蛋白1、腱生蛋白-C和富含半胱氨酸的酸性分泌蛋白诱导中间黏附状态，如红色箭头所示。每种黏附状态对细胞行为的意义标注在细胞下方。弱黏附状态与重塑过程中正在经历凋亡的细胞或正在进行胞质分裂的细胞相符。强黏附状态是分化的静止细胞的特征，而处于中间黏附状态的细胞则包括那些在伤口愈合过程中参与损伤应答或在形态发生过程中参与组织重塑的细胞。
