Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice.
FEBS Lett
; 595(22): 2756-2767, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34693525
ABSTRACT
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Músculo Esquelético
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ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático
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Acoplamento Excitação-Contração
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Proteínas de Membrana
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Proteínas do Tecido Nervoso
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2021
Tipo de documento:
Article