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

    Research output: Contribution to journalArticlepeer-review

    308 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

    • General

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