An APPL1/Akt signaling complex regulates dendritic spine and synapse formation in hippocampal neurons

摘要: The formation and plasticity of dendritic spines synapses, which are poorly understood on a molecular level, critical for cognitive functions, such as learning memory. adaptor protein containing PH domain, PTB leucine zipper motif (APPL1) is emerging regulator various cellular processes in non-neuronal cells, but its function the nervous system not well understood. Here, we show that APPL1 localizes to synapses regulates development these structures hippocampal neurons. Knockdown endogenous using siRNA led significant decrease number this defect could be rescued by expression siRNA-resistant APPL1. Expression exogenous increased spine synaptic density amount surface GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Deletion C-terminal phosphotyrosine binding domain APPL1, binds serine/threonine kinase Akt, resulted density, suggesting role Akt regulating structures. Consistent with this, knockdown or dominant negative dramatic synapse formation. In addition, active effects were dependent indicating an effector regulation processes. Moreover, signaling modulates through p21-activated (PAK). Thus, our results indicate PAK point effectors function.