Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD-95

Charych, EI, Akum BF, Goldberg JS, Jornsten RJ, Rongo C, Zheng JQ, Firestein BL.  2006.  

Journal:

J Neurosci

Volume Number:

26

Pages:

10164-76

Abstract:

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.

Notes:

Charych, Erik IAkum, Barbara FGoldberg, Joshua SJornsten, Rebecka JRongo, ChristopherZheng, James QFirestein, Bonnie LR01 NS36241/NS/NINDS NIH HHS/United StatesR01 NS42023/NS/NINDS NIH HHS/United StatesComparative StudyResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.United StatesThe Journal of neuroscience : the official journal of the Society for NeuroscienceJ Neurosci. 2006 Oct 4;26(40):10164-76.

Related External URL:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17021172
Citation:
Charych, EI, Akum BF, Goldberg JS, Jornsten RJ, Rongo C, Zheng JQ, Firestein BL.  2006.  Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD-95. J Neurosci. 26:10164-76.