Open AccessReversible lysine fatty acylation of an anchoring protein mediates adipocyte adrenergic signaling
Author(s) -
Rushita A. Bagchi,
Emma Robinson,
Tianjing Hu,
Ji Cao,
Jun Young Hong,
Charles A. Tharp,
Hanan Qasim,
Kathleen M. Gavin,
Julie Pires Da Silva,
Jennifer L. Major,
Bradley K. McConnell,
Edward Seto,
Hening Lin,
Timothy A. McKinsey
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2119678119
Subject(s) - myristoylation , g protein coupled receptor , palmitoylation , microbiology and biotechnology , lysine , signal transduction , biology , protein kinase a , biochemistry , g protein , marcks , chemistry , phosphorylation , amino acid , enzyme , cysteine
Significance Recently, histone deacetylase 11 (HDAC11) was shown to function as an enzyme that removes lipids such as myristoyl groups from lysines in proteins, yet only one substrate of HDAC11 has been reported. Here, we define gravin-α/A kinase–anchoring protein 12 as a second HDAC11 substrate. By demyristoylating gravin-α in adipocytes, HDAC11 prevents β-adrenergic receptors (β-ARs), which are G protein–coupled receptors (GPCRs), from translocating to membrane microdomains that are required for downstream protective signaling by protein kinase A (PKA). These findings demonstrate a role for reversible lysine myristoylation in the control of GPCR signaling and lay the foundation for developing therapeutics for obesity based on enhancing β-AR signaling in adipose tissue by manipulating the HDAC11:gravin-α axis.