Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cadherins / metabolism
-
Carrier Proteins / metabolism
-
Cells, Cultured
-
Cytoskeletal Proteins / deficiency
-
Cytoskeletal Proteins / genetics
-
Cytoskeletal Proteins / metabolism*
-
Electric Stimulation
-
Fetus
-
Hippocampus / metabolism
-
Hippocampus / ultrastructure
-
Male
-
Membrane Proteins
-
Mice
-
Mice, Transgenic
-
Microscopy, Electron
-
Presynaptic Terminals / metabolism*
-
Presynaptic Terminals / ultrastructure
-
Protein Structure, Tertiary / physiology
-
Pyramidal Cells / metabolism
-
Pyramidal Cells / ultrastructure
-
Rats
-
Synaptic Membranes / metabolism
-
Synaptic Membranes / ultrastructure
-
Synaptic Transmission / physiology*
-
Synaptic Vesicles / metabolism*
-
Synaptic Vesicles / ultrastructure
-
Trans-Activators / deficiency
-
Trans-Activators / genetics
-
Trans-Activators / metabolism*
-
Vesicular Transport Proteins
-
beta Catenin
Substances
-
CTNNB1 protein, mouse
-
Cadherins
-
Carrier Proteins
-
Ctnnb1 protein, rat
-
Cytoskeletal Proteins
-
Lin7a protein, mouse
-
Membrane Proteins
-
Trans-Activators
-
Vesicular Transport Proteins
-
beta Catenin