Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy
| Autor: | Baojie Li, Peiquan Zhao, Yong Cang, Yi-Han Chen, Hao Jia, Huijuan Liu, Tielin Zhou, Helene Thibault, Jing Li, Lin He, Stephen P. Goff, Deyong Jia, Sharon Boast, Marielle Scherrer-Crosbie |
|---|---|
| Přispěvatelé: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL) |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Lipoylation [SDV]Life Sciences [q-bio] Cardiomyopathy Biology Eye Mice 03 medical and health sciences 0302 clinical medicine Palmitoylation Internal medicine Calcium-binding protein Chlorocebus aethiops medicine Animals Protein palmitoylation Phosphorylation Palmitoyl acyltransferase 030304 developmental biology 0303 health sciences Multidisciplinary Calcium-Binding Proteins Protein phosphatase 1 Biological Sciences medicine.disease 3. Good health Phospholamban Endocrinology Echocardiography COS Cells cardiovascular system lipids (amino acids peptides and proteins) Cardiomyopathies Carrier Proteins Acyltransferases 030217 neurology & neurosurgery |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2015, 112 (51), pp.15666-71. ⟨10.1073/pnas.1518368112⟩ |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | International audience; Protein palmitoylation regulates many aspects of cell function and is carried out by acyl transferases that contain zf-DHHC motifs. The in vivo physiological function of protein palmitoylation is largely unknown. Here we generated mice deficient in the acyl transferase Aph2 (Ablphilin 2 or zf-DHHC16) and demonstrated an essential role for Aph2 in embryonic/postnatal survival, eye development, and heart development. Aph2(-/-) embryos and pups showed cardiomyopathy and cardiac defects including bradycardia. We identified phospholamban, a protein often associated with human cardiomyopathy, as an interacting partner and a substrate of Aph2. Aph2-mediated palmitoylation of phospholamban on cysteine 36 differentially alters its interaction with PKA and protein phosphatase 1 alpha, augmenting serine 16 phosphorylation, and regulates phospholamban pentamer formation. Aph2 deficiency results in phospholamban hypophosphorylation, a hyperinhibitory form. Ablation of phospholamban in Aph2(-/-) mice histologically and functionally alleviated the heart defects. These findings establish Aph2 as a critical in vivo regulator of cardiac function and reveal roles for protein palmitoylation in the development of other organs including eyes. |
| Databáze: | OpenAIRE |
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