Spinophilin regulates the formation and function of dendritic spines

Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophil in knockout mice, we provide evidence that spinophilin modulates both gluta matergic synaptic transmission and dendritic morphology, The ability of pro tein phosphatase-1 to regulate the activity of alpha-amino-3-hydroxy-5-meth yl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) recepto rs was reduced in spinophilin knockout mice. Consistent with altered glutam atergic transmission, spinophilin-deficient mice showed reduced long-term d epression and exhibited resistance to kainate-induced seizures and neuronal apoptosis. In addition, deletion of the spinophilin gene caused a marked i ncrease in spine density during development in vivo as well as altered filo podial formation in cultured neurons. In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines.