Neuronatin promotes SERCA uncoupling and its expression is altered in skeletal muscles of high-fat diet-fed mice

被引：28
作者：
Braun, Jessica L. [1 ,2 ,3 ]
Teng, Allen C. T. [4 ,5 ]
Geromella, Mia S. [1 ,2 ,3 ]
Ryan, Chantal R. [3 ,6 ]
Fenech, Rachel K. [3 ,6 ]
MacPherson, Rebecca E. K. [3 ,6 ]
Gramolini, Anthony O. [4 ,5 ]
Fajardo, Val A. [1 ,2 ,3 ]
机构：
[1] Brock Univ, Dept Kinesiol, 1812 Sir Isaac Brock Way, St Catharines, ON L2S 3A1, Canada
[2] Brock Univ, Ctr Bone & Muscle Hlth, St Catharines, ON, Canada
[3] Brock Univ, Ctr Neurosci, St Catharines, ON, Canada
[4] Univ Toronto, Dept Physiol, Toronto, ON, Canada
[5] Ted Rogers Ctr Heart Res, Translat Biol & Engn Program, Toronto, ON, Canada
[6] Brock Univ, Dept Hlth Sci, St Catharines, ON, Canada
来源：
FEBS LETTERS | 2021年 / 595卷 / 22期
基金：
加拿大自然科学与工程研究理事会;
关键词：
calcium transport; forskolin; metabolism; obesity; sarcolipin; sarcoplasmic reticulum; SARCOPLASMIC-RETICULUM CA2+-ATPASE; CA2+ TRANSPORT; HEAT-PRODUCTION; METABOLIC-RATE; CALCIUM-TRANSPORT; MESSENGER-RNA; SARCOLIPIN; PROTEIN; PUMP; PHOSPHOLAMBAN;
D O I：
10.1002/1873-3468.14213
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：2756 / 2767
页数：12
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