PMID- 17553425 OWN - NLM STAT- MEDLINE DCOM- 20070731 LR - 20191210 IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 54 IP - 5 DP - 2007 Jun 7 TI - Activity-regulated N-cadherin endocytosis. PG - 771-85 AB - 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. FAU - Tai, Chin-Yin AU - Tai CY AD - Division of Biology 114-96, California Institute of Technology, Pasadena, CA 91125, USA. FAU - Mysore, Shreesh P AU - Mysore SP FAU - Chiu, Cindy AU - Chiu C FAU - Schuman, Erin M AU - Schuman EM LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Cadherins) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (beta Catenin) SB - IM MH - Animals MH - Animals, Newborn MH - COS Cells MH - Cadherins/*metabolism MH - Cell Membrane/metabolism MH - Chlorocebus aethiops MH - Dendritic Spines/*metabolism/ultrastructure MH - Endocytosis/*physiology MH - Hippocampus/cytology/*growth & development/*metabolism MH - Humans MH - Mice MH - Microscopy, Confocal MH - Mutation/genetics MH - Neuronal Plasticity/physiology MH - Organ Culture Techniques MH - Patch-Clamp Techniques MH - Protein Binding/physiology MH - Protein Transport/physiology MH - Rats MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Synapses/*metabolism MH - Synaptic Transmission/physiology MH - beta Catenin/genetics/metabolism EDAT- 2007/06/08 09:00 MHDA- 2007/08/01 09:00 CRDT- 2007/06/08 09:00 PHST- 2006/11/02 00:00 [received] PHST- 2007/03/23 00:00 [revised] PHST- 2007/05/09 00:00 [accepted] PHST- 2007/06/08 09:00 [pubmed] PHST- 2007/08/01 09:00 [medline] PHST- 2007/06/08 09:00 [entrez] AID - S0896-6273(07)00347-9 [pii] AID - 10.1016/j.neuron.2007.05.013 [doi] PST - ppublish SO - Neuron. 2007 Jun 7;54(5):771-85. doi: 10.1016/j.neuron.2007.05.013.