Revach Or-Yam, Grosheva Inna, Geiger Benjamin
Departments of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
J Cell Sci. 2020 Oct 22;133(20):jcs244848. doi: 10.1242/jcs.244848.
Integrin adhesions are a structurally and functionally diverse family of transmembrane, multi-protein complexes that link the intracellular cytoskeleton to the extracellular matrix (ECM). The different members of this family, including focal adhesions (FAs), focal complexes, fibrillar adhesions, podosomes and invadopodia, contain many shared scaffolding and signaling 'adhesome' components, as well as distinct molecules that perform specific functions, unique to each adhesion form. In this Hypothesis, we address the pivotal roles of mechanical forces, generated by local actin polymerization or actomyosin-based contractility, in the formation, maturation and functionality of two members of the integrin adhesions family, namely FAs and invadopodia, which display distinct structures and functional properties. FAs are robust and stable ECM contacts, associated with contractile stress fibers, while invadopodia are invasive adhesions that degrade the underlying matrix and penetrate into it. We discuss here the mechanisms, whereby these two types of adhesion utilize a similar molecular machinery to drive very different - often opposing cellular activities, and hypothesize that early stages of FAs and invadopodia assembly use similar biomechanical principles, whereas maturation of the two structures, and their 'adhesive' and 'invasive' functionalities require distinct sources of biomechanical reinforcement.
整合素黏附是一类结构和功能多样的跨膜多蛋白复合物家族，它将细胞内细胞骨架与细胞外基质（ECM）相连。该家族的不同成员，包括黏着斑（FAs）、黏着小体、纤维状黏附、足体和侵袭性伪足，包含许多共享的支架和信号“黏附体”成分，以及执行特定功能的独特分子，这些分子对于每种黏附形式而言都是独一无二的。在本假说中，我们探讨了由局部肌动蛋白聚合或基于肌动球蛋白的收缩性产生的机械力在整合素黏附家族的两个成员（即FAs和侵袭性伪足）的形成、成熟和功能中所起的关键作用，这两个成员具有不同的结构和功能特性。FAs是与收缩性应力纤维相关的强大而稳定的ECM接触点，而侵袭性伪足是能够降解并穿透下方基质的侵袭性黏附结构。我们在此讨论这两种黏附类型利用相似分子机制驱动截然不同（通常是相反）的细胞活动的机制，并推测FAs和侵袭性伪足组装的早期阶段使用相似的生物力学原理，而这两种结构的成熟及其“黏附”和“侵袭”功能需要不同的生物力学增强来源。
