RhoA regulation in space and time

RhoGTPases are well known for being controllers of cell cytoskeleton and share common features in the way they act and are controlled. These include their switch from GDP to GTP states, their regulations by different guanine exchange factors (GEFs), GTPase-activating proteins and guanosine dissociation inhibitors (GDIs), and their similar structure of active sites/membrane anchors. These very similar features often lead to the common consideration that the differences in their biological effects mainly arise from the different types of regulators and specific effectors associated with each GTPase. Focusing on data obtained through biosensors, live cell microscopy and recent optogenetic approaches, we highlight in this review that the regulation of RhoA appears to depart from Cdc42 and Rac1 modes of regulation through its enhanced lability at the plasma membrane. RhoA presents a high dynamic turnover at the membrane that is regulated not only by GDIs but also by GEFs, effectors and a possible soluble conformational state. This peculiarity of RhoA regulation may be important for the specificities of its functions, such as the existence of activity waves or its putative dual role in the initiation of protrusions and contractions.

Automated summary

RhoGTPases have common features in their action and regulation, including switching between GDP and GTP states, regulation by various factors, and similar structure. This review focuses on the regulation of RhoA, which appears to differ from Cdc42 and Rac1 in terms of its enhanced instability at the plasma membrane. RhoA has a high dynamic turnover at the membrane regulated by GDIs, GEFs, effectors, and a possible soluble conformation. This peculiarity may be important for the specific functions of RhoA.