The ARHGDIA gene encodes the Rho-GDI alpha protein, which is responsible for maintaining Rho GTPases in their inactive state by inhibiting the dissociation of GDP (guanine diphosphate) from these molecules . This inhibition is essential for controlling the activity of Rho proteins such as CDC42, RAC1, and RHOA .
Rho-GDI alpha functions by binding to the GDP-bound form of Rho GTPases, preventing their activation. This binding retains the Rho proteins in an inactive cytosolic pool, regulating their stability and protecting them from degradation . Additionally, Rho-GDI alpha is actively involved in the recycling and distribution of activated Rho GTPases within the cell .
The activity of Rho-GDI alpha is vital for various cellular processes. It regulates the actin cytoskeleton, which is crucial for cell shape, motility, and division . Moreover, the protein’s role in maintaining Rho GTPases in an inactive state is essential for proper cellular signaling and function .
Alterations in the expression of ARHGDIA have been associated with several diseases, including nephrotic syndrome type 8 and genetic steroid-resistant nephrotic syndrome . Furthermore, changes in Rho-GDI alpha expression have been observed in various cancers, where it is linked to the malignant phenotype, including increased migration, invasion, metastasis, and resistance to anticancer agents .