Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice
| Autor: | Anthony O. Gramolini, Jessica L. Braun, Rebecca E. K. MacPherson, Val A. Fajardo, Rachel K. Fenech, Chantal R. Ryan, Allen C. T. Teng, Mia S. Geromella |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty SERCA Biophysics Nerve Tissue Proteins Diet High-Fat Biochemistry Sarcoplasmic Reticulum Calcium-Transporting ATPases Adenylyl cyclase 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Downregulation and upregulation Structural Biology Internal medicine Genetics medicine Animals Humans Calcium Signaling Muscle Skeletal Molecular Biology Excitation Contraction Coupling 030304 developmental biology 0303 health sciences Chemistry Endoplasmic reticulum Colforsin Membrane Proteins Cell Biology Phospholamban Calcium ATPase Sarcolipin Mice Inbred C57BL Endocrinology HEK293 Cells cardiovascular system Neuronatin 030217 neurology & neurosurgery |
| Zdroj: | FEBS lettersReferences. 595(22) |
| ISSN: | 1873-3468 |
| Popis: | Neuronatin (NNAT) is a transmembrane protein in the endoplasmic reticulum involved in metabolic regulation. It shares sequence homology with sarcolipin (SLN), which negatively regulates the sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) that maintains energy homeostasis in muscles. Here, we examined whether NNAT could uncouple the Ca2+ transport activity of SERCA from ATP hydrolysis, similarly to SLN. NNAT significantly reduced Ca2+ uptake without altering SERCA activity, ultimately lowering the apparent coupling ratio of SERCA. This effect of NNAT was reversed by the adenylyl cyclase activator forskolin. Furthermore, soleus muscles from high fat diet (HFD)-fed mice showed a significant downregulation in NNAT content compared with chow-fed mice, whereas an upregulation in NNAT content was observed in fast-twitch muscles from HFD- versus chow- fed mice. Therefore, NNAT is a SERCA uncoupler in cells and may function in adaptive thermogenesis. |
| Databáze: | OpenAIRE |
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