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Science 17 November 2000:
Vol. 290. no. 5495, pp. 1364 - 1368
DOI: 10.1126/science.290.5495.1364
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Reports

PSD-95 Involvement in Maturation of Excitatory Synapses

Alaa El-Din El-Husseini,1* Eric Schnell,2* Dane M. Chetkovich,13 Roger A. Nicoll,2 David S. Bredt1dagger

PSD-95 is a neuronal PDZ protein that associates with receptors and cytoskeletal elements at synapses, but whose function is uncertain. We found that overexpression of PSD-95 in hippocampal neurons can drive maturation of glutamatergic synapses. PSD-95 expression enhanced postsynaptic clustering and activity of glutamate receptors. Postsynaptic expression of PSD-95 also enhanced maturation of the presynaptic terminal. These effects required synaptic clustering of PSD-95 but did not rely on its guanylate kinase domain. PSD-95 expression also increased the number and size of dendritic spines. These results demonstrate that PSD-95 can orchestrate synaptic development and are suggestive of roles for PSD-95 in synapse stabilization and plasticity.

1 Department of Physiology,
2 Department of Cellular and Molecular Pharmacology, and
3 Department of Neurology, University of California, San Francisco 94143, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed: E-mail: bredt{at}itsa.ucsf.edu

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J Neurophysiol 90, 3950-3957
   Abstract »    Full Text »    PDF »
The fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95.
P. K. Todd, K. J. Mack, and J. S. Malter (2003)
PNAS 100, 14374-14378
   Abstract »    Full Text »    PDF »
Targeted Protein Degradation and Synapse Remodeling by an Inducible Protein Kinase.
D. T. S. Pak and M. Sheng (2003)
Science 302, 1368-1373
   Abstract »    Full Text »    PDF »
Kalirin, a Multifunctional Rho Guanine Nucleotide Exchange Factor, Is Necessary for Maintenance of Hippocampal Pyramidal Neuron Dendrites and Dendritic Spines.
X.-M. Ma, J. Huang, Y. Wang, B. A. Eipper, and R. E. Mains (2003)
J. Neurosci. 23, 10593-10603
   Abstract »    Full Text »    PDF »
Lipid- and protein-mediated multimerization of PSD-95: implications for receptor clustering and assembly of synaptic protein networks.
K. S. Christopherson, N. T. Sweeney, S. E. Craven, R. Kang, A. E.-D. El-Husseini, and D. S. Bredt (2003)
J. Cell Sci. 116, 3213-3219
   Abstract »    Full Text »    PDF »
Impaired NMDA Receptor-Mediated Postsynaptic Function and Blunted NMDA Receptor-Dependent Persistent Pain in Mice Lacking Postsynaptic Density-93 Protein.
Y.-X. Tao, G. Rumbaugh, G.-D. Wang, R. S. Petralia, C. Zhao, F. W. Kauer, F. Tao, M. Zhuo, R. J. Wenthold, S. N. Raja, et al. (2003)
J. Neurosci. 23, 6703-6712
   Abstract »    Full Text »    PDF »
Drebrin-Dependent Actin Clustering in Dendritic Filopodia Governs Synaptic Targeting of Postsynaptic Density-95 and Dendritic Spine Morphogenesis.
H. Takahashi, Y. Sekino, S. Tanaka, T. Mizui, S. Kishi, and T. Shirao (2003)
J. Neurosci. 23, 6586-6595
   Abstract »    Full Text »    PDF »
Inhibition of Dendritic Spine Morphogenesis and Synaptic Transmission by Activity-Inducible Protein Homer1a.
C. Sala, K. Futai, K. Yamamoto, P. F. Worley, Y. Hayashi, and M. Sheng (2003)
J. Neurosci. 23, 6327-6337
   Abstract »    Full Text »    PDF »
Postsynaptic Density-95 Mimics and Occludes Hippocampal Long-Term Potentiation and Enhances Long-Term Depression.
V. Stein, D. R. C. House, D. S. Bredt, and R. A. Nicoll (2003)
J. Neurosci. 23, 5503-5506
   Abstract »    Full Text »    PDF »
Synapse-Associated Protein-97 Isoform-Specific Regulation of Surface AMPA Receptors and Synaptic Function in Cultured Neurons.
G. Rumbaugh, G.-M. Sia, C. C. Garner, and R. L. Huganir (2003)
J. Neurosci. 23, 4567-4576
   Abstract »    Full Text »    PDF »
PSD-95 regulates NMDA receptors in developing cerebellar granule neurons of the rat.
G. Losi, K. Prybylowski, Z. Fu, J. Luo, R. J Wenthold, and S. Vicini (2003)
J. Physiol. 548, 21-29
   Abstract »    Full Text »    PDF »
Synchronized Formation and Remodeling of Postsynaptic Densities: Long-Term Visualization of Hippocampal Neurons Expressing Postsynaptic Density Proteins Tagged with Green Fluorescent Protein.
T. Ebihara, I. Kawabata, S. Usui, K. Sobue, and S. Okabe (2003)
J. Neurosci. 23, 2170-2181
   Abstract »    Full Text »    PDF »
Estrogen Stimulates Postsynaptic Density-95 Rapid Protein Synthesis via the Akt/Protein Kinase B Pathway.
K. T. Akama and B. S. McEwen (2003)
J. Neurosci. 23, 2333-2339
   Abstract »    Full Text »    PDF »


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