title: The ARMS/Kidins220 scaffold protein modulates synaptic transmission.
abstract: Activity-dependent changes of synaptic connections are facilitated by a variety of scaffold proteins, including PSD-95, Shank, SAP97 and GRIP, which serve to organize ion channels, receptors and enzymatic activities and to coordinate the actin cytoskeleton. The abundance of these scaffold proteins raises questions about the functional specificity of action of each protein. Here we report that basal synaptic transmission is regulated in an unexpected manner by the ankyrin repeat-rich membrane-spanning (ARMS/Kidins220) scaffold protein. In particular, decreases in the levels of ARMS/Kidins220 in vivo led to an increase in basal synaptic transmission in the hippocampus, without affecting paired pulse facilitation. One explanation to account for the effects of ARMS/Kidins220 is an interaction with the AMPA receptor subunit, GluA1, which could be observed after immunoprecipitation. Importantly, shRNA and cell surface biotinylation experiments indicate that ARMS/Kidins220 levels have an impact on GluA1 phosphorylation and localization. Moreover, ARMS/Kidins220 is a negative regulator of AMPAR function, which was confirmed by inward rectification assays. These results provide evidence that modulation of ARMS/Kidins220 levels can regulate basal synaptic strength in a specific manner in hippocampal neurons.
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA. arevalojc@usal.es
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Arévalo
authors.forename: Synphen H
authors.initials: SH
authors.lastname: Wu
authors.forename: Takuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yano
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Milner
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.forename: Ipe
authors.initials: I
authors.lastname: Ninan
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.forename: Moses V
authors.initials: MV
authors.lastname: Chao
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C544017:Kidins220 protein, mouse