Role of beta-catenin in synaptic vesicle localization and presynaptic assembly.
Cadherins and catenins are thought to promote adhesion between pre and postsynaptic elements in the brain. Here we show a role for beta-catenin in localizing the reserved pool of vesicles at presynaptic sites. Deletion of beta-catenin in hippocampal pyramidal neurons in vivo resulted in a reduction in the number of reserved pool vesicles per synapse and an impaired response to prolonged repetitive stimulation. This corresponded to a dispersion of vesicles along the axon in cultured neurons. Interestingly, these effects are not due to beta-catenin's involvement in cadherin-mediated adhesion or wnt signaling. Instead, beta-catenin modulates vesicle localization via its PDZ binding domain to recruit PDZ proteins such as Veli to cadherin at synapses. This study defines a specific role for cadherins and catenins in synapse organization beyond their roles in mediating cell adhesion.
Bamji
Shernaz X
SX
Howard Hughes Medical Institute and Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
Shimazu
Kazuhiro
K
Kimes
Nikole
N
Huelsken
Joerg
J
Birchmeier
Walter
W
Lu
Bai
B
Reichardt
Louis F
LF
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D005333:Fetus; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D033921:Vesicular Transport Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; C114670:Lin7a protein, mouse; D008565:Membrane Proteins; D015534:Trans-Activators; D033921:Vesicular Transport Proteins; D051176:beta Catenin