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The Journal of Neuroscience, October 4, 2006, 26(40):10164-10176; doi:10.1523/JNEUROSCI.2379-06.2006
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Cellular/Molecular
Activity-Independent Regulation of Dendrite Patterning by Postsynaptic Density Protein PSD-95
Erik I. Charych,1 * Barbara F. Akum,1,5 * Joshua S. Goldberg,1 Rebecka J. Jörnsten,2 Christopher Rongo,3,4 James Q. Zheng,6 andBonnie L. Firestein1 Departments of 1Cell Biology and Neuroscience, 2Statistics, and 3Genetics, 4The Waksman Institute, and 5Molecular Biosciences Graduate Program, Rutgers University, Piscataway, New Jersey 08854-8082, and 6Neuroscience and Cell Biology, The University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854
Correspondence should be addressed to Dr. Bonnie L. Firestein, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082. Email: firestein{at}biology.rutgers.edu
Dendritic morphology determines many aspects of neuronal function, including action potential propagation and information processing. However, the question remains as to how distinct neuronal dendrite branching patterns are established. Here, we report that postsynaptic density-95 (PSD-95), a protein involved in dendritic spine maturation and clustering of synaptic signaling proteins, plays a novel role in regulating dendrite outgrowth and branching, independent of its synaptic functions. In immature neurons, overexpression of PSD-95 decreases the proportion of primary dendrites that undergo additional branching, resulting in a marked reduction of secondary dendrite number. Conversely, knocking down PSD-95 protein in immature neurons increases secondary dendrite number. The effect of PSD-95 is activity-independent and is antagonized by cypin, a nonsynaptic protein that regulates PSD-95 localization. Binding of cypin to PSD-95 correlates with formation of stable dendrite branches. Finally, overexpression of PSD-95 in COS-7 cells disrupts microtubule organization, indicating that PSD-95 may modulate microtubules to regulate dendritic branching. Whereas many factors have been identified which regulate dendrite number, our findings provide direct evidence that proteins primarily involved in synaptic functions can also play developmental roles in shaping how a neuron patterns its dendrite branches.
Key words: PSD-95; dendrite branching; hippocampal neurons; cypin; microtubule; activity-independent
Received June 5, 2006; revised Aug. 10, 2006; accepted Aug. 29, 2006.
Correspondence should be addressed to Dr. Bonnie L. Firestein, Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082. Email: firestein{at}biology.rutgers.edu
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