Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Torino 10060, Italy; Department of Oncology, University of Torino School of Medicine, Candiolo, Torino 10060, Italy.
Candiolo Cancer Institute, Fondazione del Piemonte per l'Oncologia (FPO) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Candiolo, Torino 10060, Italy; Department of Oncology, University of Torino School of Medicine, Candiolo, Torino 10060, Italy.
Matrix Biol. 2022 Sep;112:62-71. doi: 10.1016/j.matbio.2022.08.003. Epub 2022 Aug 9.
In metazoans, cell adhesion to the extracellular matrix (ECM) drives the development, functioning, and repair of different tissues, organs, and systems. Disruption or dysregulation of cell-to-ECM adhesion promote the initiation and progression of several diseases, such as bleeding, immune disorders and cancer. Integrins are major ECM transmembrane receptors, whose function depends on both allosteric changes and exo-endocytic traffic, which carries them to and from the plasma membrane. In apico-basally polarized cells, asymmetric adhesion to the ECM is maintained by continuous targeting of the plasma membrane by vesicles coming from the trans Golgi network and carrying ECM proteins. Active integrin-bound ECM is indeed endocytosed and replaced by the exocytosis of fresh ECM. Such vesicular traffic is finely driven by the teamwork of microtubules (MTs) and their associated kinesin and dynein motors. Here, we review the main cytoskeletal actors involved in the control of the spatiotemporal distribution of active integrins and their ECM ligands, highlighting the key role of the synchronous (ant)agonistic cooperation between MT motors transporting vesicular cargoes, in the same or in opposite direction, in the regulation of traffic logistics, and the establishment of epithelial and endothelial cell polarity.
在多细胞生物中,细胞与细胞外基质(ECM)的黏附驱动着不同组织、器官和系统的发育、功能和修复。细胞与 ECM 黏附的破坏或失调会促进多种疾病的发生和发展,如出血、免疫紊乱和癌症。整合素是 ECM 的主要跨膜受体,其功能不仅取决于变构变化,还取决于外排-内吞运输,该运输将它们带到和离开质膜。在顶底极性细胞中,来自高尔基体反面管网的携带 ECM 蛋白的小泡持续靶向质膜,从而维持对 ECM 的不对称黏附。事实上,活性整合素结合的 ECM 被内吞,然后由新鲜 ECM 的胞吐作用取代。这种小泡运输是由微管(MTs)及其相关的驱动蛋白和动力蛋白马达的协同作用精细驱动的。在这里,我们综述了参与控制活性整合素及其 ECM 配体时空分布的主要细胞骨架因子,强调了同步(抗)agonistic 协作在调节运输物流和建立上皮细胞和内皮细胞极性方面的关键作用,这些协作由沿相同或相反方向运输囊泡货物的 MT 马达之间的同步(抗)agonistic 合作来实现。