TY - JOUR
T1 - Spinophilin regulates the formation and function of dendritic spines
AU - Feng, Jian
AU - Yan, Zhen
AU - Ferreira, Adriana
AU - Tomizawa, Kazuhito
AU - Liauw, Jason A.
AU - Zhuo, Min
AU - Allen, Patrick B.
AU - Ouimet, Charles C.
AU - Greengard, Paul
PY - 2000/8/1
Y1 - 2000/8/1
N2 - Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transmission and dendritic morphology. The ability of protein phosphatase-1 to regulate the activity of α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors was reduced in spinophilin knockout mice. Consistent with altered glutamatergic transmission, spinophilin-deficient mice showed reduced long-term depression and exhibited resistance to kainate-induced seizures and neuronal apoptosis. In addition, deletion of the spinophilin gene caused a marked increase in spine density during development in vivo as well as altered filopodial formation in cultured neurons. In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines.
AB - Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transmission and dendritic morphology. The ability of protein phosphatase-1 to regulate the activity of α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors was reduced in spinophilin knockout mice. Consistent with altered glutamatergic transmission, spinophilin-deficient mice showed reduced long-term depression and exhibited resistance to kainate-induced seizures and neuronal apoptosis. In addition, deletion of the spinophilin gene caused a marked increase in spine density during development in vivo as well as altered filopodial formation in cultured neurons. In conclusion, spinophilin appears to be required for the regulation of the properties of dendritic spines.
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U2 - 10.1073/pnas.97.16.9287
DO - 10.1073/pnas.97.16.9287
M3 - Article
C2 - 10922077
AN - SCOPUS:0034254991
SN - 0027-8424
VL - 97
SP - 9287
EP - 9292
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -