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PNAS 97 (16): 9287-9292

Copyright © 2000 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / NEUROBIOLOGY

Spinophilin regulates the formation and function of dendritic spines

Jian Feng*,{dagger}, Zhen Yan*, Adriana Ferreira{ddagger}, Kazuhito Tomizawa*, Jason A. Liauw§, Min Zhuo§, Patrick B. Allen*, Charles C. Ouimet, and Paul Greengard*

*Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10021; {ddagger}Department of Cell and Molecular Biology, Northwestern Institute for Neuroscience, Northwestern University, Chicago, IL 60611; §Department of Anesthesiology, Department of Anatomy and Neurobiology, Washington University, St. Louis, MO 63110; and Program in Neuroscience, Florida State University, Tallahassee, FL 32306

Contributed by Paul Greengard

Accepted for publication May 30, 2000.

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-isoxazolepropionic 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.

{dagger} To whom reprint requests should be addressed at: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, NY 10021. E-mail: fengji{at}rockvax.rockefeller.edu.

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