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

Shane E. Tillo, Wei-Hong Xiong, Maho Takahashi, Sheng Miao, Adriana L. Andrade, Dale A. Fortin, Guang Yang, Maozhen Qin, Barbara F. Smoody, Philip Stork, Haining Zhong

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)617-629
Number of pages13
JournalCell Reports
Volume19
Issue number3
DOIs
StatePublished - Apr 18 2017

Fingerprint

Cyclic AMP-Dependent Protein Kinases
Catalytic Domain
Membranes
Substrates
Protein Kinase C
Phosphotransferases
Protein Kinases
Neurons
Chemical activation
Association reactions
Proteins
Neuronal Plasticity
Dendrites
Cyclic AMP
Plasticity
Membrane Proteins

Keywords

  • activation-dependent membrane association
  • AMPA/NMDA current radio
  • cAMP-dependent kinase
  • diffusion
  • mEPSC
  • mobility
  • myristoylation
  • PKA
  • synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates. / Tillo, Shane E.; Xiong, Wei-Hong; Takahashi, Maho; Miao, Sheng; Andrade, Adriana L.; Fortin, Dale A.; Yang, Guang; Qin, Maozhen; Smoody, Barbara F.; Stork, Philip; Zhong, Haining.

In: Cell Reports, Vol. 19, No. 3, 18.04.2017, p. 617-629.

Research output: Contribution to journalArticle

Tillo, Shane E. ; Xiong, Wei-Hong ; Takahashi, Maho ; Miao, Sheng ; Andrade, Adriana L. ; Fortin, Dale A. ; Yang, Guang ; Qin, Maozhen ; Smoody, Barbara F. ; Stork, Philip ; Zhong, Haining. / Liberated PKA Catalytic Subunits Associate with the Membrane via Myristoylation to Preferentially Phosphorylate Membrane Substrates. In: Cell Reports. 2017 ; Vol. 19, No. 3. pp. 617-629.
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AU - Andrade, Adriana L.

AU - Fortin, Dale A.

AU - Yang, Guang

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AU - Stork, Philip

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