Trio
The Trio group unites the large multidomain proteins TRIO and kalirin, which combine two Rho guanine nucleotide exchange factor domains with a C-terminal CAMK-like serine/threonine kinase domain. The first GEF domain activates RhoA and the second activates Rac1, coordinating actin remodeling during axon outgrowth, neuronal migration, and synapse development, while the kinase domain, though catalytically competent in TRIO, remains functionally enigmatic. Kalirin-7 dominates postsynaptic spines and regulates dendritic morphology. Human genetics connect TRIO variants to neurodevelopmental disorders with intellectual disability and autism features, and KALRN variants to schizophrenia and coronary artery disease, reflecting dual neuronal and vascular roles.
