Afadin Is Required for Maintenance of Dendritic Structure and Excitatory Tone

• Published in: The Journal of biological chemistry Vol. 287; no. 43; pp. 35964 - 35974
• Main Authors: Srivastava, Deepak P., Copits, Bryan A., Xie, Zhong, Huda, Rafiq, Jones, Kelly A., Mukherji, Srishti, Cahill, Michael E., VanLeeuwen, Jon-Eric, Woolfrey, Kevin M., Rafalovich, Igor, Swanson, Geoffrey T., Penzes, Peter
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.10.2012; American Society for Biochemistry and Molecular Biology
• Subjects: AF-6; alpha Catenin - genetics; alpha Catenin - metabolism; Animals; beta Catenin - genetics; beta Catenin - metabolism; Cadherins - genetics; Cadherins - metabolism; Cells, Cultured; Dendrite; Dendrites - genetics; Dendrites - metabolism; Dendritic Arborization; Dendritic Field; Dendritic Spine; Gene Expression Regulation - physiology; GluA2; Glutamate Receptors; Glutamate Receptors Ionotropic (AMPA, NMDA); LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurobiology; Rats; Rats, Sprague-Dawley; Receptors, AMPA - genetics; Receptors, AMPA - metabolism; Synapses; Synapses - genetics; Synapses - metabolism; Synaptic Plasticity; AF-6; Dendritic Arborization; Glutamate Receptors Ionotropic (AMPA, NMDA); Dendritic Field; Glutamate Receptors; Synaptic Plasticity; GluA2; Dendritic Spine; Synapses; Dendrite
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M112.363358

The dendritic field of a neuron, which is determined by both dendritic architecture and synaptic strength, defines the synaptic input of a cell. Once established, a neuron's dendritic field is thought to remain relatively stable throughout a cell's lifetime. Perturbations in a dendritic structure or excitatory tone of a cell and thus its dendritic field are cellular alterations thought to be correlated with a number of psychiatric disorders. Although several proteins are known to regulate the development of dendritic arborization, much less is known about the mechanisms that maintain dendritic morphology and synaptic strength. In this study, we find that afadin, a component of N-cadherin·β-catenin·α-N-catenin adhesion complexes, is required for the maintenance of established dendritic arborization and synapse number. We further demonstrate that afadin directly interacts with AMPA receptors and that loss of this protein reduces the surface expression of GluA1- and GluA2-AMPA receptor subunits. Collectively, these data suggest that afadin is required for the maintenance of dendritic structure and excitatory tone. Background: Active molecular mechanisms that maintain the dendritic field of neurons are unclear. Results: Afadin maintains dendritic arborization, synapse number, and excitatory transmission and interacts with AMPA-GluA2 receptors. Conclusion: Afadin is required for the maintenance of dendritic structure and synaptic transmission. Significance: Elucidating the mechanisms required for the active maintenance of dendritic fields may provide insight into the pathophysiology of neuropsychiatric disorders.