About ARHGDI / Rho GDP Dissociation Inhibitor:
The Rho GDP Dissociation Inhibitor (ARHGDI) is a protein that regulates the actin cytoskeleton. This protein binds to the GTP-bound form of Rho and prevents activation of Rac1 by dissociating it from its activators. ARHGDI functions as a molecular brake on Rac1 activation and can regulate:
●Invasion through these mechanisms.
ARHGDI Mechanism of Action
This protein is a molecular brake that regulates the activation of Rac. ARHGDI binds to the GTP-bound form of Rho and prevents activation by dissociating it from its activators: PAK kinase or PIPKIα/β complexes. This interaction with activated Rho disrupts the membrane localization of PAK, which in turn prevents its activation by PAK kinase.
Rho GDP Dissociation Inhibitor Structure
ARHGDI is a small monomer that has an N-terminal domain and a C-terminal stalk.
ARHGDI Cellular Location
It associates with the cytoplasmic cell membranes, specifically at focal adhesions and regions of pseudopod extension from motile cells. The location where this protein localizes is crucial because it is at the cell adhesion and motility sites.
Sites in Which Arhgdi Regulates Rac Activation
Focal Adhesions - Focal adhesions are areas where integrins bind to extracellular proteins, such as fibronectin or laminins. Thus, the focal point of adhesion is where the cell binds to its substrate.
Regions of Pseudopod Extension From Motile Cells- These regions on a moving cell contain focal adhesions and actin stress fibres that protrude out from the cellular body. These extensions are necessary because they are where new cell contacts with substrates usually form.
Rho GDP Dissociation Inhibitor Interactions
ARHGDI interacts with the GTP-bound form of Rho, preventing activation by dissociating it from its activators.
Conclusively, the Rho GDP Dissociation Inhibitor (ARHGDI) is a protein that regulates Rac activation. Its localization sites are essential because it's at areas where new cell contacts with substrates usually form.