当前位置: X-MOL 学术Nature › 论文详情
TLR9 and beclin 1 crosstalk regulates muscle AMPK activation in exercise.
Nature ( IF 42.778 ) Pub Date : 2020-02-12 , DOI: 10.1038/s41586-020-1992-7
Yang Liu,Phong T Nguyen,Xun Wang,Yuting Zhao,Corbin E Meacham,Zhongju Zou,Bogdan Bordieanu,Manuel Johanns,Didier Vertommen,Tobias Wijshake,Herman May,Guanghua Xiao,Sanae Shoji-Kawata,Mark H Rider,Sean J Morrison,Prashant Mishra,Beth Levine

The activation of adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle coordinates systemic metabolic responses to exercise1. Autophagy-a lysosomal degradation pathway that maintains cellular homeostasis2-is upregulated during exercise, and a core autophagy protein, beclin 1, is required for AMPK activation in skeletal muscle3. Here we describe a role for the innate immune-sensing molecule Toll-like receptor 9 (TLR9)4, and its interaction with beclin 1, in exercise-induced activation of AMPK in skeletal muscle. Mice that lack TLR9 are deficient in both exercise-induced activation of AMPK and plasma membrane localization of the GLUT4 glucose transporter in skeletal muscle, but are not deficient in autophagy. TLR9 binds beclin 1, and this interaction is increased by energy stress (glucose starvation and endurance exercise) and decreased by a BCL2 mutation3,5 that blocks the disruption of BCL2-beclin 1 binding. TLR9 regulates the assembly of the endolysosomal phosphatidylinositol 3-kinase complex (PI3KC3-C2)-which contains beclin 1 and UVRAG-in skeletal muscle during exercise, and knockout of beclin 1 or UVRAG inhibits the cellular AMPK activation induced by glucose starvation. Moreover, TLR9 functions in a muscle-autonomous fashion in ex vivo contraction-induced AMPK activation, glucose uptake and beclin 1-UVRAG complex assembly. These findings reveal a heretofore undescribed role for a Toll-like receptor in skeletal-muscle AMPK activation and glucose metabolism during exercise, as well as unexpected crosstalk between this innate immune sensor and autophagy proteins.
更新日期:2020-02-13

 

全部期刊列表>>
物理学研究前沿热点精选期刊推荐
chemistry
自然职位线上招聘会
欢迎报名注册2020量子在线大会
化学领域亟待解决的问题
材料学研究精选新
GIANT
ACS ES&T Engineering
ACS ES&T Water
ACS Publications填问卷
屿渡论文,编辑服务
阿拉丁试剂right
南昌大学
王辉
南方科技大学
彭小水
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
天合科研
x-mol收录
X-MOL
苏州大学
廖矿标
深圳湾
试剂库存
down
wechat
bug