NDLI: Palmitoylation Targets AKAP79 Protein to Lipid Rafts and Promotes Its Regulation of Calcium-sensitive Adenylyl Cyclase Type 8*

Content Provider	PubMed Central
Author	Ilse, Delint-ramirez Willoughby, Debbie Hammond, Gerald V. R. Ayling, Laura J. Cooper, Dermot M. F.
Copyright Year	2011
Abstract	PKA anchoring proteins (AKAPs) optimize the efficiency of cAMP signaling by clustering interacting partners. Recently, AKAP79 has been reported to directly bind to adenylyl cyclase type 8 (AC8) and to regulate its responsiveness to store-operated Ca2+ entry (SOCE). Although AKAP79 is well targeted to the plasma membrane via phospholipid associations with three N-terminal polybasic regions, recent studies suggest that AKAP79 also has the potential to be palmitoylated, which may specifically allow it to target the lipid rafts where AC8 resides and is regulated by SOCE. In this study, we have addressed the role of palmitoylation of AKAP79 using a combination of pharmacological, mutagenesis, and cell biological approaches. We reveal that AKAP79 is palmitoylated via two cysteines in its N-terminal region. This palmitoylation plays a key role in targeting the AKAP to lipid rafts in HEK-293 cells. Mutation of the two critical cysteines results in exclusion of AKAP79 from lipid rafts and alterations in its membrane diffusion behavior. This is accompanied by a loss of the ability of AKAP79 to regulate SOCE-dependent AC8 activity in intact cells and decreased PKA-dependent phosphorylation of raft proteins, including AC8. We conclude that palmitoylation plays a key role in the targeting and action of AKAP79. This novel property of AKAP79 adds an unexpected regulatory and targeting option for AKAPs, which may be exploited in the cellular context.
Related Links	http://dx.doi.org/10.1074/jbc.m111.243899
Ending Page	32975
Page Count	14
Starting Page	32962
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	38
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-09-23
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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Palmitoylation Targets AKAP79 Protein to Lipid Rafts and Promotes Its Regulation of Calcium-sensitive Adenylyl Cyclase Type 8

Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8.

Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry

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Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry

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Palmitoylation Targets AKAP79 Protein to Lipid Rafts and Promotes Its Regulation of Calcium-sensitive Adenylyl Cyclase Type 8*

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Palmitoylation Targets AKAP79 Protein to Lipid Rafts and Promotes Its Regulation of Calcium-sensitive Adenylyl Cyclase Type 8

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