Spinophilin regulates the formation and function of dendritic spines

Jian Feng, Zhen Yan, Adriana Ferreira, Kazuhito Tomizawa, Jason A. Liauw, Min Zhuo, Patrick B. Allen, Charles C. Ouimet, Paul Greengard

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289 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)9287-9292
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number16
DOIs
Publication statusPublished - Aug 1 2000

ASJC Scopus subject areas

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    Feng, J., Yan, Z., Ferreira, A., Tomizawa, K., Liauw, J. A., Zhuo, M., Allen, P. B., Ouimet, C. C., & Greengard, P. (2000). Spinophilin regulates the formation and function of dendritic spines. Proceedings of the National Academy of Sciences of the United States of America, 97(16), 9287-9292. https://doi.org/10.1073/pnas.97.16.9287