RAC1 GTPase cycle

RAC1 GTPase cycle This pathway catalogues RAC1 guanine nucleotide exchange factors (GEFs), GTPase activator proteins (GAPs), GDP dissociation inhibitors (GDIs) and RAC1 effectors (reviewed by Payapilli and Malliri 2018). RAC1 is one of the three best characterized RHO GTPases, the other two being RHOA and CDC42. RAC1 regulates the cytoskeleton and the production of reactive oxygen species (ROS) (Acevedo and Gonzalez-Billault 2018) and is involved in cell adhesion and cell migration (Marei and Malliri 2017). RAC1 is involved in neuronal development (de Curtis et al. 2014). In neurons, RAC1 activity is regulated by synaptic activation and RAC1-mediated changes in actin cytoskeleton are implicated in dendritic spine morphogenesis, which plays a role in memory formation and learning (Tajeda-Simon 2015; Costa et al. 2020). RAC1 is involved in metabolic regulation of pancreatic islet β-cells and in diabetes pathophysiology (Kowluru 2017; Kowluru et al. 2020). RAC1-mediated activation of NOX2 contributes to mitochondrial damage and the development of retinopathy in patients with diabetes (Sahajpal et al. 2019). RAC1 is important for exercise and contraction-stimulated glucose uptake in skeletal muscles (Sylow et al. 2014). RAC1 plays an important role in the maintenance of intestinal barrier integrity under physiological conditions and during tissue repair after resolution of colitis. Toxins of many diarrhea-causing bacteria target RAC1 (Kotelevets and Chastre 2020). RAC1 is important for skin homeostasis and wound healing and is involved in the pathogenesis of psoriasis (Winge and Marinkovich 2019). RAC1 is essential to vascular homeostasis and chronically elevated RAC1 signaling contributes to vascular pathology (Marinkovic et al. 2015). RAC1 hyperactivation, mutation and copy-number gain are frequently observed in solid tumors (Zou et al. 2017; De et al. 2019; De et al. 2020; Cannon et al. 2020; Kotelevets and Chastre 2020).