Adenylyl cyclase anchoring by a kinase anchor protein AKAP5 (AKAP79/150) is important for postsynaptic β-adrenergic signaling

Mingxu Zhang, Tommaso Patriarchi, Ivar S. Stein, Hai Qian, Lucas Matt, Minh Nguyen, Yang Kevin Xiang, Johannes W Hell

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17918-17931
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number24
DOIs
StatePublished - Jun 14 2013

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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