PLD1 promotes dendritic spine morphogenesis via activating PKD1

Dendritic spines on the dendrites of pyramidal neurons are one of the most important components for excitatory synapses, where excitatory information exchanges and integrates. The defects of dendritic spine development have been closely connected with many nervous system diseases including autism, intellectual disability and so forth. Based on our previous studies, we here report a new functional signaling link between phospholipase D1 (PLD1) and protein kinase D1 (PKD1) in dendritic spine morphogenesis. Coimmunoprecipitation assays showed that PLD1 associates with PKD1. A series of knocking down and rescuing experiments demonstrated that PLD1 acts upstream of PKD1 in positively regulating dendritic spine morphogenesis. Using PLD1 inhibitor, we found that PLD1 activates PKD1 to promote dendritic spine morphogenesis. Thus, we further reveal the roles of the two different enzymes in neuronal development. •PLD1 directly interacts with PKD1.•PLD1 functions upstream of PKD1 to promote dendritic spine development.•The enzymatic activity of PLD1 is required to promote dendritic spine development.