in drosophila and humans found that Ras suppressor 1 (Rsu1), a regulator of the actin cytoskeleton, affects alcohol consumption across species (Ojelade et al., 2015). Rsu1 acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton and is required for normal alcohol preference in Drosophila. Genetic variation in RSU1 is associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults (Ojelade et al., 2015). Collectively, PKNOX2 is a novel candidate gene associated with alcohol and substance dependence as well as alcohol consumption and likely mediates these phenotypes by alterations in the actin cytoskeleton that modulates synaptic plasticity particularly at dendritic spines (Mulholland and Chandler, 2007).
