DHHC5 Mediates β-Adrenergic Signaling in Cardiomyocytes by Targeting Gα Proteins
| Autor: | Jessica J. Chen, Askar M. Akimzhanov, Autumn N. Marsden, Darren Boehning, C. Anthony Scott |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Gs alpha subunit
Lipoylation Gi alpha subunit Biophysics Stimulation 03 medical and health sciences 0302 clinical medicine Adrenergic Agents Palmitoylation Humans Myocytes Cardiac Palmitoyl acyltransferase Receptor 030304 developmental biology 0303 health sciences Gene knockdown Chemistry technology industry and agriculture Articles Protein subcellular localization prediction GTP-Binding Protein alpha Subunits Cell biology lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery Acyltransferases Signal Transduction |
| Zdroj: | Biophysical Journal |
| ISSN: | 1542-0086 0006-3495 |
| Popis: | S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. Here, we investigated whether β-adrenergic stimulation of cardiomyocytes led to stimulus-dependent palmitoylation of downstream signaling proteins. We found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. We identified the plasma membrane-localized palmitoyl acyltransferase DHHC5 as an important mediator of the stimulus-dependent palmitoylation in cardiomyocytes. Knockdown of DHHC5 showed that this enzyme is necessary for palmitoylation of Gαs, Gαi, and functional responses downstream of β-adrenergic stimulation. A palmitoylation assay with purified components revealed that Gαs and Gαi are direct substrates of DHHC5. Finally, we provided evidence that the C-terminal tail of DHHC5 can be palmitoylated in response to stimulation and such modification is important for its dynamic localization and function in the plasma membrane. Our results reveal that DHHC5 is a central regulator of signaling downstream of β-adrenergic receptors in cardiomyocytes. |
| Databáze: | OpenAIRE |
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