GSBS Student Publications


Activity-regulated N-cadherin endocytosis

UMMS Affiliation

Graduate School of Biomedical Sciences; Division of Biology 114-96



Document Type


Medical Subject Headings

Animals; Animals, Newborn; COS Cells; Cadherins; Cell Membrane; Cercopithecus aethiops; Dendritic Spines; Endocytosis; Hippocampus; Humans; Mice; Microscopy, Confocal; Mutation; Neuronal Plasticity; Organ Culture Techniques; Patch-Clamp Techniques; Protein Binding; Protein Transport; Rats; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Transmission; beta Catenin


Life Sciences | Medicine and Health Sciences


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.

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Citation: Neuron. 2007 Jun 7;54(5):771-85. Link to article on publisher's site

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