cAMP signaling in neurons: Patterns of neuronal expression and intracellular localization for a novel protein, AKAP 150, that anchors the regulatory subunit of cAMP-dependent protein kinase IIβ

S. B. Glantz, J. A. Amat, C. S. Rubin

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

In mammalian brain, physiological signals carried by cyclic AMP (cAMP) seem to be targeted to effector sites via the tethering of cAMP-dependent protein kinase IIβ (PKAIIβ) to intracellular structures. Recently characterized A kinase anchor proteins (AKAPs) are probable mediators of the sequestration of PKAIIβ because they contain a high-affinity binding site for the regulatory subunit (RIIβ) of the kinase and a distinct intracellular targeting domain. To establish a cellular basis for this targeting mechanism, we have employed immunocytochemistry to 1) identify the types of neurons that are enriched in AKAPs, 2) determine the primary intracellular location of the anchor protein, and 3) demonstrate that an AKAP and RIIβ are coenriched and colocalized in neurons that utilize the adenylate cyclase-cyclic AMP- dependent protein kinase (PKA) signaling pathway. Antibodies directed against rat brain AKAP 150 were used to elucidate the regional, cellular and intracellular distribution of a prototypic anchor protein in the CNS. AKAP 150 is abundant in Purkinje cells and in neurons of the olfactory bulb, basal ganglia, cerebral cortex, and other forebrain regions. In contrast, little AKAP 150 is detected in neurons of the thalamus, hypothalamus, midbrain, and hindbrain. A high proportion of total AKAP 150 is concentrated in primary branches of dendrites, where it is associated with microtubules. We also discovered that the patterns of accumulation and localization of RIIβ (and PKAIIβ) in brain are similar to those of AKAP 150. The results suggest that bifunctional AKAP 150 tethers PKAIIβ to the dendritic cytoskeleton, thereby creating a discrete target site for the reception and propagation of signals carried by cAMP.

Original languageEnglish (US)
Pages (from-to)1215-1228
Number of pages14
JournalMolecular biology of the cell
Volume3
Issue number11
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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