title: Adenylyl cyclase anchoring by a kinase anchor protein AKAP5 (AKAP79/150) is important for postsynaptic β-adrenergic signaling.
abstract: Recent evidence indicates that the A kinase anchor protein AKAP5 (AKAP79/150) interacts not only with PKA but also with various adenylyl cyclase (AC) isoforms. However, the physiological relevance of AC-AKAP5 binding is largely unexplored. We now show that postsynaptic targeting of AC by AKAP5 is important for phosphorylation of the AMPA-type glutamate receptor subunit GluA1 on Ser-845 by PKA and for synaptic plasticity. Phosphorylation of GluA1 on Ser-845 is strongly reduced (by 70%) under basal conditions in AKAP5 KO mice but not at all in D36 mice, in which the PKA binding site of AKAP5 (i.e. the C-terminal 36 residues) has been deleted without affecting AC association with GluA1. The increase in Ser-845 phosphorylation upon β-adrenergic stimulation is much more severely impaired in AKAP5 KO than in D36 mice. In parallel, long term potentiation induced by a 5-Hz/180-s tetanus, which mimics the endogenous θ-rhythm and depends on β-adrenergic stimulation, is only modestly affected in acute forebrain slices from D36 mice but completely abrogated in AKAP5 KO mice. Accordingly, anchoring of not only PKA but also AC by AKAP5 is important for regulation of postsynaptic functions and specifically AMPA receptor activity.
authors: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.
authors: Mingxu
authors: M
authors: Zhang
authors: Tommaso
authors: T
authors: Patriarchi
authors: Ivar S
authors: IS
authors: Stein
authors: Hai
authors: H
authors: Qian
authors: Lucas
authors: L
authors: Matt
authors: Minh
authors: M
authors: Nguyen
authors: Yang K
authors: YK
authors: Xiang
authors: Johannes W
authors: JW
authors: Hell
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology; D007545:Isoproterenol / Q000494:pharmacology; D017774:Long-Term Potentiation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D057907:Post-Synaptic Density / Q000201:enzymology*; D011433:Propranolol / Q000494:pharmacology; D016548:Prosencephalon / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D054758:A Kinase Anchor Proteins; D000262:Adenylyl Cyclases; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D017868:Cyclic AMP-Dependent Protein Kinases; D007545:Isoproterenol; D011433:Propranolol; D021122:Protein Subunits; D018091:Receptors, AMPA; D018343:Receptors, Adrenergic, beta-2; C520665:Akap5 protein, mouse; C121100:adenylyl cyclase 6; C419510:adenylyl cyclase type V; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Adenylate Cyclase (Adenylyl Cyclase); Adrenergic Receptor; Akap; Glutamate Receptors Ionotropic (AMPA, NMDA); Long Term Potentiation; Protein Kinase A (PKA)
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