The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.
AuthorBraun, Jessica L
Copeland, Emily N
Geromella, Mia S
Baranowski, Ryan W
MacPherson, Rebecca E K
Fajardo, Val A
Journal titleFrontiers in endocrinology
Publication Begin page957182
MetadataShow full item record
AbstractThe sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump is responsible for the transport of Ca2+ from the cytosol into the sarcoplasmic reticulum at the expense of ATP, making it a regulator of both muscle relaxation and muscle-based energy expenditure. Neurogranin (Ng) is a small protein that negatively regulates calcineurin signaling. Calcineurin is Ca2+/calmodulin dependent phosphatase that promotes the oxidative fibre type in skeletal muscle and regulates muscle-based energy expenditure. A recent study has shown that calcineurin activation reduces SERCA Ca2+ transport efficiency, ultimately raising energy expenditure. Since the biomedical view of obesity states that it arises as an imbalance between energy intake and expenditure which favors the former, we questioned whether heterozygous Ng deletion (Ng+/- ) would reduce SERCA efficiency and increase energy expenditure in female mice fed a high-fat diet (HFD). Young (3-4-month-old) female wild type (WT) and Ng+/- mice were fed a HFD for 12 weeks with their metabolic profile being analyzed using metabolic cages and DXA scanning, while soleus SERCA efficiency was measured using SERCA specific Ca2+ uptake and ATPase activity assays. Ng+/- mice showed significantly less cage ambulation compared to WT mice but this did not lead to any added weight gain nor changes in daily energy expenditure, glucose or insulin tolerance despite a similar level of food intake. Furthermore, we observed significant reductions in SERCA's apparent coupling ratio which were associated with significant reductions in SERCA1 and phospholamban content. Thus, our results show that Ng regulates SERCA pump efficiency, and future studies should further investigate the potential cellular mechanisms.
- Phospholamban deficiency does not alter skeletal muscle SERCA pumping efficiency or predispose mice to diet-induced obesity.
- Authors: Gamu D, Juracic ES, Fajardo VA, Rietze BA, Tran K, Bombardier E, Tupling AR
- Issue date: 2019 Mar 1
- Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice.
- Authors: Braun JL, Teng ACT, Geromella MS, Ryan CR, Fenech RK, MacPherson REK, Gramolini AO, Fajardo VA
- Issue date: 2021 Nov
- Sarcolipin protein interaction with sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) is distinct from phospholamban protein, and only sarcolipin can promote uncoupling of the SERCA pump.
- Authors: Sahoo SK, Shaikh SA, Sopariwala DH, Bal NC, Periasamy M
- Issue date: 2013 Mar 8
- Sarcolipin Is a Key Determinant of the Basal Metabolic Rate, and Its Overexpression Enhances Energy Expenditure and Resistance against Diet-induced Obesity.
- Authors: Maurya SK, Bal NC, Sopariwala DH, Pant M, Rowland LA, Shaikh SA, Periasamy M
- Issue date: 2015 Apr 24
- Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload.
- Authors: Fajardo VA, Rietze BA, Chambers PJ, Bellissimo C, Bombardier E, Quadrilatero J, Tupling AR
- Issue date: 2017 Aug 1