Postsynaptic Y654 dephosphorylation of β-catenin modulates presynaptic vesicle turnover through increased n-cadherin-mediated transsynaptic signaling.
Synaptic adhesion molecules, which coordinately control structural and functional changes at both sides of synapses, are important for synaptogenesis and synaptic plasticity. Because they physically form homophilic or heterophilic adhesions across synaptic junctions, these molecules can initiate transsynaptic communication in both anterograde and retrograde directions. Using optical imaging approaches, we investigated whether an increase in postsynaptic N-cadherin could correspondingly alter the function of connected presynaptic terminals. Postsynaptic expression of β-catenin Y654F, a phosphorylation-defective form with enhanced binding to N-cadherin, is sufficient to increase postsynaptic surface levels of N-cadherin and consequently promote presynaptic reorganizations. Such reorganizations include increases in the densities of the synaptic vesicle protein, Synaptotagmin 1 and the active zone scaffold protein, Bassoon, the number of active boutons and the size of the total recycling vesicle pool. In contrast, synaptic vesicle turnover is significantly impaired, preventing the exchange of synaptic vesicles with adjacent boutons. Together, N-cadherin-mediated retrograde signaling, governed by phosphoregulation of postsynaptic β-catenin Y654, coordinately modulates presynaptic vesicle dynamics to enhance synaptic communication in mature neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 61-74, 2017.
Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 11490, Taiwan.|Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Chin-Yi
CY
Chen
Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica, and Graduate Institute of Life Sciences, National Defense Center, Taipei 11490, Taiwan.
Yi-Ting
YT
Chen
Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
Jen-Yeu
JY
Wang
Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan.
Yi-Shuian
YS
Huang
Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 11490, Taiwan.|Institute of Biologics, Development Center for Biotechnology, New Taipei City, 22180, Taiwan.
Chin-Yin
CY
Tai
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D061848:Optical Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C113688:Bsn protein, rat; D015820:Cadherins; C495268:Ctnnb1 protein, rat; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C494312:Syt1 protein, rat; D051176:beta Catenin
N-cadherin; active boutons; total recycling vesicles; transsynaptic signaling; vesicle dynamics; β-catenin