Abstract
Purkinje cell synapses in the cerebellar cortex require tight coordination between receptor trafficking and cytoskeletal remodeling to sustain synaptogenesis, structural plasticity, and motor learning. The glutamate δ2 receptor (GluRδ2), a hallmark component of parallel fiber-Purkinje cell synapses, depends on intracellular scaffolding proteins for proper localization and signaling. PIST (GOPC), a neuronal PDZ domain-containing protein originally identified as a selective GluRδ2-interacting partner, has emerged as an important regulator of receptor trafficking and synaptic organization. Here, we reveal a previously unrecognized biochemical function of PIST as an actin-binding protein. Biochemical and cellular analyses show that PIST directly associates with filamentous actin in a concentration-dependent manner, suppresses actin polymerization in vitro, and co-localizes with actin in neuronal cells. Mechanistically, this interaction is mediated by a WH2-like motif within PIST. PIST may function as a molecular link between the actin cytoskeleton and the protein trafficking machinery, suggesting a potential new mechanism underlying the coordinated regulation of receptor transport and synaptic structural plasticity in neurons.