Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions

Wei-Hong Xiong, Maozhen Qin, Haining Zhong

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Myristoylation is a posttranslational modification that plays diverse functional roles in many protein species. The myristate moiety is considered insufficient for protein-membrane associations unless additional membrane-affinity motifs, such as a stretch of positively charged residues, are present. Here, we report that the electrically neutral N-terminal fragment of the protein kinase A catalytic subunit (PKA-C), in which myristoylation is the only functional motif, is sufficient for membrane association. This myristoylation can associate a fraction of PKA-C molecules or fluorescent proteins (FPs) to the plasma membrane in neuronal dendrites. The net neutral charge of the PKA-C N terminus is evolutionally conserved, even though its membrane affinity can be readily tuned by changing charges near the myristoylation site. The observed membrane association, while moderate, is sufficient to concentrate PKA activity at the membrane by nearly 20-fold and is required for PKA regulation of AMPA receptors at neuronal synapses. Our results indicate that myristoylation may be sufficient to drive functionally significant membrane association in the absence of canonical assisting motifs. This provides a revised conceptual base for the understanding of how myristoylation regulates protein functions.

Original languageEnglish (US)
Article numbere2021658118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Apr 13 2021
Externally publishedYes


  • CAMP-dependent kinase
  • Fractional membrane association
  • Myristoylation
  • PKA

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Myristoylation alone is sufficient for PKA catalytic subunits to associate with the plasma membrane to regulate neuronal functions'. Together they form a unique fingerprint.

Cite this