A kinase anchor protein 75 targets regulatory (RII) subunits of cAMP- dependent protein kinase II to the cortical actin cytoskeleton in non- neuronal cells

Ying Li, Christopher Ndubuka, Charles S. Rubin

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Neuronal A kinase anchor protein (AKAP) homologs, such as AKAPs 75 and 150, tether cAMP-dependent protein kinase II (PKAII) isoforms to the postsynaptic cytoskeleton, thereby creating target sites for cAMP action. These AKAPs, which bind regulatory subunits (RIIs) of PKAII, are also expressed in certain non-neuronal cells. Non-neuronal cell lines that stably express wild type and mutant AKAP75 transgenes were generated to investigate the extraneuronal function of AKAPs. In non-neuronal cells, AKAP75 accumulates selectively in the actin-rich, cortical cytoskeleton in close proximity with the plasma membrane. AKAP75 efficiently sequesters cytoplasmic RIIα and RIIβ (PKAII isoforms) and translocates these polypeptides to the cell cortex. Two structural modules in AKAP75, T1 (residues 27-48), and T2 (residues 77-100), are essential for targeting AKAP75-RII complexes to the cortical cytoskeleton. Deletions or amine acid substitutions in T1 and/or T2 result in the dispersion of both AKAP75 and RII subunits throughout the cytoplasm. AKAP75 is co-localized with F-actin and fodrin in the cortical cytoskeleton. Incubation of cells with 5 μM cytochalasin D disrupts actin filaments and dissociates actin from the cell cortex. In contrast, the bulk of AKAP75 and fodrin remain associated with the cortical region of cytochalasin D-treated cells. Thus, targeting of AKAP75 does not depend upon direct binding with F-actin. Rather, AKAP75 (like fodrin) may be associated with a multiprotein complex that interacts with integral plasma membrane proteins.

Original languageEnglish (US)
Pages (from-to)16862-16869
Number of pages8
JournalJournal of Biological Chemistry
Volume271
Issue number28
DOIs
StatePublished - Jul 30 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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