Tooney P A, Agrez M V, Burns G F
Cancer Research Unit, Faculty of Medicine, University of Newcastle, New South Wales, Australia.
Immunol Cell Biol. 1993 Apr;71 ( Pt 2):131-9. doi: 10.1038/icb.1993.14.
A model for cell movement is presented. It is suggested that cells do not migrate on collagen using their VLA (very late antigen) integrins that bind this extracellular matrix protein. Rather, the cells utilize alpha v integrins to bind endogenously produced fibronectin, which binds to the underlying collagen. It is envisaged that cells proceed by a process of engagement and disengagement of alpha v integrins to the extracellular matrix, somewhat analogous to the motion of a monkey climbing a tree. Secretion of isoforms of the adhesion modulator, thrombospondin, regulates disengagement of the integrin from its ligand in migrating cells. The integrin disengagement signal is mediated by thrombospondin cross-linking the alpha v integrin to an integrin accessory molecule and thus activating protein kinases. The cross-linked receptor complex undergoes recycling back along actin stress fibres, guided by the integrin beta-subunit. After endocytosis and protein sorting the alpha v integrin is transported back to the leading edge off migrating cells in vesicles guided by the tubulin-binding capabilities of an integrin accessory molecule. Direct attachment to collagen required for processes, such as matrix contraction, is mediated by VLA integrins which displace alpha v integrins from points of attachment during integrin recycling, possibly through an alpha v beta 1 intermediary receptor.
本文提出了一种细胞运动模型。研究表明，细胞并非利用与细胞外基质蛋白胶原蛋白结合的VLA（极晚期抗原）整合素来在胶原蛋白上迁移。相反，细胞利用αv整合素来结合内源性产生的纤连蛋白，而纤连蛋白与下方的胶原蛋白结合。据设想，细胞通过αv整合素与细胞外基质的结合和脱离过程来进行迁移，这有点类似于猴子爬树的动作。黏附调节因子血小板反应蛋白亚型的分泌调节迁移细胞中整合素与其配体的脱离。整合素脱离信号由血小板反应蛋白介导，血小板反应蛋白将αv整合素与一个整合素辅助分子交联，从而激活蛋白激酶。交联的受体复合物在整合素β亚基的引导下，沿着肌动蛋白应力纤维进行回收循环。在胞吞作用和蛋白质分选后，αv整合素在一个整合素辅助分子的微管结合能力引导下，通过囊泡被转运回迁移细胞的前沿。诸如基质收缩等过程所需的与胶原蛋白的直接附着，由VLA整合素介导，在整合素循环过程中，VLA整合素可能通过αvβ1中间受体将αv整合素从附着点取代。
