Rho GTPases

Rho GTPases regulate many aspects of actin dynamics and are involved in processes that are dependent on changes to cell morphology and movement, including phagocytosis, mitosis and wound healing. To enable cells to respond to external cues, these processes require rapidly activated and spatio-temporally regulated signaling networks, of which Rho GTPases are a key component.

Three Rho GTPases have been widely studied: Cdc42, Rac1 and RhoA. For these enzymes, over 60 targets have been identified including Rho-Kinases (ROCKs), phospholipases and ion channels. As with other small GTPases, the activity of Rho GTPases is regulated by GEFs and GAPs. Inactive Rho GTPases are sequestered to the cytosol by Rho-specific guanine nucleotide dissociation inhibitors (GDIs), preventing their membrane association. Of the 20 Rho family members, 10 have been identified as being constitutively bound to GTP and so are constitutively active and have alternative regulation mechanisms.

Neuronal dendrite spine growth is dependent on Rho GTPases. This process is key to synaptic plasticity and long-term potentiation/depression, which underly learning and memory. RhoA and Cdc42 are activated by CamKII, which is activated by the influx of Ca²⁺ through NMDA receptors upon glutamate binding.

External sources of pharmacological information for Rho GTPases :

• BJP Guide

Rho GTPases Gene Data