title: Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior.
abstract: Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO hippocampus is increased as a functional compensation for gene deletion, while such compensation is absent in the prefrontal cortex. Thus, there are brain region-specific effects of cGKII KO on AMPAR trafficking, which could affect animal behavior. Here, we show that GluA1 phosphorylation levels differ in various brain regions, and specific behaviors are altered according to region-specific changes in GluA1 phosphorylation. Moreover, we identified distinct regulations of phosphatases in different brain regions, leading to regional heterogeneity of GluA1 phosphorylation in the KO brain. Our work demonstrates region-specific changes in GluA1 phosphorylation in cGKII KO mice and corresponding effects on cognitive performance. We also reveal distinct regulation of phosphatases in different brain region in which region-specific effects of kinase gene KO arise and can selectively alter animal behavior.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA seonil.kim@nyumc.org edward.ziff@nyumc.org.
authors.forename: Seonil
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Pick
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA.
authors.forename: Sinedu
authors.initials: S
authors.lastname: Abera
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA.
authors.forename: Latika
authors.initials: L
authors.lastname: Khatri
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA Department of Pharmacology and Physiology, Fluminense Federal University, Niteroi 24210-130, Brazil.
authors.forename: Danielle D P
authors.initials: DD
authors.lastname: Ferreira
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA Department of Pharmacology and Physiology, Fluminense Federal University, Niteroi 24210-130, Brazil.
authors.forename: Matheus F
authors.initials: MF
authors.lastname: Sathler
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA Center for Neural Science, New York University, New York 10012, USA.
authors.forename: Sage L
authors.initials: SL
authors.lastname: Morison
authors.affiliation: Technical University of Munich, Munich 80802, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York 10016, New York, USA seonil.kim@nyumc.org edward.ziff@nyumc.org.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D003214:Conditioning, Classical; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000503:physiopathology; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000378:metabolism; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D012903:Smell / Q000502:physiology
chemical_list: D018091:Receptors, AMPA; D062967:Cyclic GMP-Dependent Protein Kinase Type II