| First Author | Marin EP | Year | 2016 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 36 |
| Issue | 2 | Pages | 370-9 |
| PubMed ID | 26715683 | Mgi Jnum | J:246613 |
| Mgi Id | MGI:5921050 | Doi | 10.1161/ATVBAHA.115.306942 |
| Citation | Marin EP, et al. (2016) The Protein Acyl Transferase ZDHHC21 Modulates alpha1 Adrenergic Receptor Function and Regulates Hemodynamics. Arterioscler Thromb Vasc Biol 36(2):370-9 |
| abstractText | OBJECTIVE: Palmitoylation, the reversible addition of the lipid palmitate to a cysteine, can alter protein localization, stability, and function. The ZDHHC family of protein acyl transferases catalyzes palmitoylation of numerous proteins. The role of ZDHHC enzymes in intact tissue and in vivo is largely unknown. Herein, we characterize vascular functions in a mouse that expresses a nonfunctional ZDHHC21 (F233Delta). APPROACH AND RESULTS: Physiological studies of isolated aortae and mesenteric arteries from F233Delta mice revealed an unexpected defect in responsiveness to phenylephrine, an alpha1 adrenergic receptor agonist. In vivo, F233Delta mice displayed a blunted response to infusion of phenylephrine, and they were found to have elevated catecholamine levels and elevated vascular alpha1 adrenergic receptor gene expression. Telemetry studies showed that the F233Delta mice were tachycardic and hypotensive at baseline, consistent with diminished vascular tone. In biochemical studies, ZDHHC21 was shown to palmitoylate the alpha1D adrenoceptor and to interact with it in a molecular complex, thus suggesting a possible molecular mechanism by which the receptor can be regulated by ZDHHC21. CONCLUSIONS: Together, the data support a model in which ZDHHC21 F233Delta diminishes the function of vascular alpha1 adrenergic receptors, leading to reduced vascular tone, which manifests in vivo as hypotension and tachycardia. This is to our knowledge the first demonstration of a ZDHHC isoform affecting vascular function in vivo and identifies a novel molecular mode of regulation of vascular tone and blood pressure. |
