Liberated PKA Catalytic Subunits Associate with the Membrane Via Myristoylation to Preferentially Phosphorylate Membrane Substrates

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Apr 20

PMID 28423323

Citations 43

Authors

Shane E Tillo

Wei-Hong Xiong

Maho Takahashi

Sheng Miao

Adriana L Andrade

Dale A Fortin

Guang Yang

Maozhen Qin

Barbara F Smoody

Philip J S Stork

Haining Zhong

Affiliations

Soon will be listed here.

Abstract

Protein kinase A (PKA) has diverse functions in neurons. At rest, the subcellular localization of PKA is controlled by A-kinase anchoring proteins (AKAPs). However, the dynamics of PKA upon activation remain poorly understood. Here, we report that elevation of cyclic AMP (cAMP) in neuronal dendrites causes a significant percentage of the PKA catalytic subunit (PKA-C) molecules to be released from the regulatory subunit (PKA-R). Liberated PKA-C becomes associated with the membrane via N-terminal myristoylation. This membrane association does not require the interaction between PKA-R and AKAPs. It slows the mobility of PKA-C and enriches kinase activity on the membrane. Membrane-residing PKA substrates are preferentially phosphorylated compared to cytosolic substrates. Finally, the myristoylation of PKA-C is critical for normal synaptic function and plasticity. We propose that activation-dependent association of PKA-C renders the membrane a unique PKA-signaling compartment. Constrained mobility of PKA-C may synergize with AKAP anchoring to determine specific PKA function in neurons.

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