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Published online 10 July 2006. doi:10.1083/jcb.200601087
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 2, 289-299
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BDNF mobilizes synaptic vesicles and enhances synapse formation by disrupting cadherin–ß-catenin interactions

Shernaz X. Bamji, Beatriz Rico, Nikole Kimes, and Louis F. Reichardt

Neuroscience Program, Howard Hughes Medical Institute, and Department of Physiology, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Louis F. Reichardt: lfr{at}cgl.ucsf.edu

Neurons of the vertebrate central nervous system have the capacity to modify synapse number, morphology, and efficacy in response to activity. Some of these functions can be attributed to activity-induced synthesis and secretion of the neurotrophin brain-derived neurotrophic factor (BDNF); however, the molecular mechanisms by which BDNF mediates these events are still not well understood. Using time-lapse confocal analysis, we show that BDNF mobilizes synaptic vesicles at existing synapses, resulting in small clusters of synaptic vesicles "splitting" away from synaptic sites. We demonstrate that BDNF's ability to mobilize synaptic vesicle clusters depends on the dissociation of cadherin–ß-catenin adhesion complexes that occurs after tyrosine phosphorylation of ß-catenin. Artificially maintaining cadherin–ß-catenin complexes in the presence of BDNF abolishes the BDNF-mediated enhancement of synaptic vesicle mobility, as well as the longer-term BDNF-mediated increase in synapse number. Together, this data demonstrates that the disruption of cadherin–ß-catenin complexes is an important molecular event through which BDNF increases synapse density in cultured hippocampal neurons.

S.X. Bamji's present address is Dept. of Cellular and Physiological Sciences, Brain Research Centre, University of British Columbia, Vancouver, BC V6T-1Z3.

B. Rico's present address is the Institute of Neuroscience, Consejo Superior de Investigaciones Cientificas-University Miguel Hernández, 03550 San Juan, Alicante, Spain.

N. Kimes's present address is Dept. of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425.

Abbreviations used in this paper: BDNF, brain-derived neurotrophic factor; DIV, day in vitro; LTP, long-term potentiation; SV, synaptic vesicle.


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