Parrini Maria Carla, Camonis Jacques
Institut Curie, Centre de Recherche, Inserm U830; Paris, France.
Commun Integr Biol. 2011 Nov 1;4(6):772-4. doi: 10.4161/cib.17772.
The Ras proto-oncogenic proteins, prototypes of the small GTPases, work as molecular switches: they are active when bound to GTP and inactive when bound to GDP. A variety of evidence suggested that the Ras paradigm is not fully valid for the Rho-family of small GTPases. Indeed, permanent activation is not sufficient but it is rather the continuous oscillation between the GDP-bound and GTP-bound conformations (namely the GDP/GTP cycling or GTPase flux), that is required for Rho-GTPases to perform their biological functions and properly coordinate actin cytoskeleton reorganization. In our recent study, we show that Rac1 needs to cycle between the GDP and GTP states in order to efficiently control cell motility. Similarly, it was previously reported that GDP/GTP cycling is required by RhoA for cytokinesis and by Cdc42 for cell polarization. The future challenge is to understand why the GTPase flux is so important for the biological actions of Rho GTPases.
Ras原癌基因蛋白作为小GTP酶的原型，起着分子开关的作用：它们与GTP结合时处于激活状态，与GDP结合时处于失活状态。各种证据表明，Ras模式对小GTP酶的Rho家族并不完全适用。事实上，永久激活并不足够，而是GDP结合构象和GTP结合构象之间的持续振荡（即GDP/GTP循环或GTP酶通量），这是Rho-GTP酶发挥其生物学功能并正确协调肌动蛋白细胞骨架重组所必需的。在我们最近的研究中，我们表明Rac1需要在GDP和GTP状态之间循环，以便有效地控制细胞运动。同样，先前有报道称，RhoA进行胞质分裂以及Cdc42进行细胞极化都需要GDP/GTP循环。未来的挑战是理解为什么GTP酶通量对Rho GTP酶的生物学作用如此重要。
