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Free keywords:
Animals
Animals, Newborn
COS Cells
Cadherins/*metabolism
Cell Membrane/metabolism
Chlorocebus aethiops
Dendritic Spines/*metabolism/ultrastructure
Endocytosis/*physiology
Hippocampus/cytology/*growth & development/*metabolism
Humans
Mice
Microscopy, Confocal
Mutation/genetics
Neuronal Plasticity/physiology
Organ Culture Techniques
Patch-Clamp Techniques
Protein Binding/physiology
Protein Transport/physiology
Rats
Receptors, N-Methyl-D-Aspartate/metabolism
Synapses/*metabolism
Synaptic Transmission/physiology
beta Catenin/genetics/metabolism
Abstract:
Enduring forms of synaptic plasticity are thought to require ongoing regulation of adhesion molecules, such as N-cadherin, at synaptic junctions. Little is known about the activity-regulated trafficking of adhesion molecules. Here we demonstrate that surface N-cadherin undergoes a surprisingly high basal rate of internalization. Upon activation of NMDA receptors (NMDAR), the rate of N-cadherin endocytosis is significantly reduced, resulting in an accumulation of N-cadherin in the plasma membrane. Beta-catenin, an N-cadherin binding partner, is a primary regulator of N-cadherin endocytosis. Following NMDAR stimulation, beta-catenin accumulates in spines and exhibits increased binding to N-cadherin. Overexpression of a mutant form of beta-catenin, Y654F, prevents the NMDAR-dependent regulation of N-cadherin internalization, resulting in stabilization of surface N-cadherin molecules. Furthermore, the stabilization of surface N-cadherin blocks NMDAR-dependent synaptic plasticity. These results indicate that NMDAR activity regulates N-cadherin endocytosis, providing a mechanistic link between structural plasticity and persistent changes in synaptic efficacy.
