289, via neurotrophin-induced disruption of adhesion complexes. The dispersal increases synaptic density, number, and size.
Dispersal is triggered by the neurotrophin called brain-derived neurotrophic factor (BDNF), which is produced and secreted by active nerve terminals. BDNF turns on TrkB tyrosine kinase receptor to enhance synaptic communication and increase synaptic size and density.
As synapses communicate via the secretion of neurotrophin-containing presynaptic vesicles, the authors studied BDNF's effect on vesicle behavior. They found that treatment of hippocampal neurons with BDNF dispersed synaptic vesicles into the region surrounding the original synapse. The dispersal of synaptic vesicles might help to form new synapses as the clusters of mobile vesicles populate new territories, although this theory remains to be tested.
The authors next addressed how the vesicles were released by BDNF. A likely target for this neurotrophin is the cell adhesion complex formed by cadherin and catenin proteins, which the authors had shown helps to localize synaptic vesicles to the presynaptic terminals. Indeed, BDNF caused a transient increase in β-catenin phosphorylation and a decrease in the amount of β-catenin bound to cadherins, resulting in adhesion complex disruption.
Expression of a nonphosphorylatable mutant of β-catenin eliminated both disruption of the catenin–cadherin complex and synaptic vesicle dispersion. The β-catenin mutant also blocked the formation of new synapses after BDNF treatment.
Bamji et al. speculate that the mechanism they uncovered may be a general model for how other ligands and tyrosine kinase receptors influence synaptic plasticity in various neuronal cell types, such as the ephrins and Eph receptors that influence synaptogenesis and axon guidance. Given the prevalence of both tyrosine kinase receptors and catenin–cadherin complexes, they think that tyrosine kinases might regulate other cell behaviors as well through β-catenin phosphorylation.