BDNF mobilizes synaptic vesicles and enhances synapse formation by disrupting cadherin-beta-catenin interactions.
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-beta-catenin adhesion complexes that occurs after tyrosine phosphorylation of beta-catenin. Artificially maintaining cadherin-beta-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-beta-catenin complexes is an important molecular event through which BDNF increases synapse density in cultured hippocampal neurons.
Bamji
Shernaz X
SX
Neuroscience Program, Howard Hughes Medical Institute, and Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Rico
Beatriz
B
Kimes
Nikole
N
Reichardt
Louis F
LF
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism*; D004058:Diffusion / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D015820:Cadherins; D051176:beta Catenin