title: Afadin is required for maintenance of dendritic structure and excitatory tone.
abstract: 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.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. deepak.srivastava@kcl.ac.uk
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Srivastava
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Copits
authors.forename: Zhong
authors.initials: Z
authors.lastname: Xie
authors.forename: Rafiq
authors.initials: R
authors.lastname: Huda
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Jones
authors.forename: Srishti
authors.initials: S
authors.lastname: Mukherji
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cahill
authors.forename: Jon-Eric
authors.initials: JE
authors.lastname: VanLeeuwen
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Woolfrey
authors.forename: Igor
authors.initials: I
authors.lastname: Rafalovich
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D051178:alpha Catenin; D051176:beta Catenin; C507006:Afdn protein, rat; C486820:Ctnna2 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2