RhoAGTP

RhoAGTP refers to the active, GTP-bound state of the small GTPase RhoA, a member of the Rho family involved in actin cytoskeleton regulation. Like other small GTPases, RhoA cycles between an inactive GDP-bound form and an active GTP-bound form. Activation is promoted by guanine nucleotide exchange factors (GEFs) that facilitate GDP release and GTP binding; inactivation is accelerated by GTPase-activating proteins (GAPs) that stimulate GTP hydrolysis. RhoA in the GTP-bound state interacts with downstream effector proteins to transmit signals to the cytoskeleton and cell adhesion machinery.

Key effectors of RhoAGTP include ROCK1/ROCK2 (Rho-associated protein kinase) and mDia1/mDia2 (diaphanous-related formins). Activation of ROCK leads to phosphorylation of myosin light chain (MLC) and MYPT1, increasing actomyosin contractility, promoting stress fiber formation and focal adhesion maturation. Diaphanous-related formins stimulate linear actin polymerization. Through these pathways, RhoAGTP influences cell shape, polarity, motility, and cytokinesis.

RhoA is anchored to membranes by post-translational prenylation at its C-terminus (farnesyl or geranylgeranyl modification) in combination with a CAAX motif, which localizes it to the plasma membrane and endomembranes where signaling occurs. RhoGDI proteins regulate its localization by sequestering inactive or cycling RhoA in the cytosol.

Physiological roles include actin cytoskeleton remodeling, cell migration, and division. Dysregulation of RhoAGTP signaling has been linked to cancer invasion, fibrosis, and other pathologies. Experimental approaches to study RhoAGTP include pull-down assays with Rhotekin-RBD or GDP dissociation inhibitors, as well as FRET-based live-cell sensors to monitor GTP-bound RhoA in real time.