UMR144 Centre National de la Recherche Scientifique-Institut Curie, Paris, France.
J Cell Biol. 2010 Nov 1;191(3):585-98. doi: 10.1083/jcb.201002151.
Centrosome positioning is crucial during cell division, cell differentiation, and for a wide range of cell-polarized functions including migration. In multicellular organisms, centrosome movement across the cytoplasm is thought to result from a balance of forces exerted by the microtubule-associated motor dynein. However, the mechanisms regulating dynein-mediated forces are still unknown. We show here that during wound-induced cell migration, the small G protein Cdc42 acts through the polarity protein Dlg1 to regulate the interaction of dynein with microtubules of the cell front. Dlg1 interacts with dynein via the scaffolding protein GKAP and together, Dlg1, GKAP, and dynein control microtubule dynamics and organization near the cell cortex and promote centrosome positioning. Our results suggest that, by modulating dynein interaction with leading edge microtubules, the evolutionary conserved proteins Dlg1 and GKAP control the forces operating on microtubules and play a fundamental role in centrosome positioning and cell polarity.
中心体定位在细胞分裂、细胞分化以及广泛的细胞极化功能中至关重要，包括迁移。在多细胞生物中，人们认为中心体在细胞质中的运动是由微管相关马达蛋白 dynein 施加的力的平衡产生的。然而，调节 dynein 介导的力的机制仍不清楚。我们在这里表明，在创伤诱导的细胞迁移过程中，小 G 蛋白 Cdc42 通过极性蛋白Dlg1 发挥作用，调节 dynein 与细胞前缘微管的相互作用。Dlg1 通过支架蛋白 GKAP 与 dynein 相互作用，并且 Dlg1、GKAP 和 dynein 一起控制细胞皮层附近微管的动态和组织，并促进中心体定位。我们的结果表明，通过调节 dynein 与前缘微管的相互作用，进化保守的蛋白 Dlg1 和 GKAP 控制作用于微管的力，并在中心体定位和细胞极性中发挥着基本作用。
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