| First Author | Bagchi RA | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 7 | PubMed ID | 35149557 |
| Mgi Jnum | J:328502 | Mgi Id | MGI:6877006 |
| Doi | 10.1073/pnas.2119678119 | Citation | Bagchi RA, et al. (2022) Reversible lysine fatty acylation of an anchoring protein mediates adipocyte adrenergic signaling. Proc Natl Acad Sci U S A 119(7):e2119678119 |
| abstractText | N-myristoylation on glycine is an irreversible modification that has long been recognized to govern protein localization and function. In contrast, the biological roles of lysine myristoylation remain ill-defined. We demonstrate that the cytoplasmic scaffolding protein, gravin-alpha/A kinase-anchoring protein 12, is myristoylated on two lysine residues embedded in its carboxyl-terminal protein kinase A (PKA) binding domain. Histone deacetylase 11 (HDAC11) docks to an adjacent region of gravin-alpha and demyristoylates these sites. In brown and white adipocytes, lysine myristoylation of gravin-alpha is required for signaling via beta2- and beta3-adrenergic receptors (beta-ARs), which are G protein-coupled receptors (GPCRs). Lysine myristoylation of gravin-alpha drives beta-ARs to lipid raft membrane microdomains, which results in PKA activation and downstream signaling that culminates in protective thermogenic gene expression. These findings define reversible lysine myristoylation as a mechanism for controlling GPCR signaling and highlight the potential of inhibiting HDAC11 to manipulate adipocyte phenotypes for therapeutic purposes. |
