Journal
BIOPHYSICAL JOURNAL
Volume 118, Issue 4, Pages 826-835Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2019.08.018
Keywords
-
Categories
Funding
- National Institutes of Health [R01GM081685, R01GM115446]
- American Heart Association Predoctoral Fellowship [18PRE33960153]
Ask authors/readers for more resources
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 beta-adrenergic stimulation of cardiomyocytes led to stimulus-dependent palmitoylation of downstream signaling proteins. We found that beta-adrenergic stimulation led to rapidly increased G alpha s and G alpha i 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 G alpha s, G alpha i, and functional responses downstream of beta-adrenergic stimulation. A palmitoylation assay with purified components revealed that G alpha s and G alpha i 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 beta-adrenergic receptors in cardiomyocytes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available