國家衛生研究院 NHRI:Item 3990099045/12368

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12368

Title:	Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis
Authors:	Wang, WP;Wang, JY;Lin, WH;Kao, CH;Hung, MC;Teng, YC;Tsai, TF;Chi, YH
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Mutations in lamin A (LMNA) are responsible for a variety of human dystrophic and metabolic diseases. Here, we created a mouse model in which progerin, the lamin A mutant protein that causes Hutchinson-Gilford progeria syndrome (HGPS), can be inducibly overexpressed. Muscle-specific overexpression of progerin was sufficient to induce muscular dystrophy and alter whole-body energy expenditure, leading to premature death. Intriguingly, sarcolipin (Sln), an endoplasmic reticulum (ER)-associated protein involved in heat production, is upregulated in progerin-expressing and Lmna knockout (Lmna(-/-)) skeletal muscle. The depletion of Sln accelerated the early death of Lmna(-/-) mice. An examination at the molecular level revealed that progerin recruits Sln and Calnexin to the nuclear periphery. Furthermore, progerin-expressing myoblasts presented enhanced store-operated Ca2+ entry, as well as increased co-localization of STIM1 and ORAI1. These findings suggest that progerin dysregulates calcium homeostasis through an interaction with a subset of ER-associated proteins, resulting in thermogenic and metabolic abnormalities.
Date:	2019-12
Relation:	Aging Cell. 2019 Dec;Article number e13090.
Link to:	http://dx.doi.org/10.1111/acel.13090
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1474-9718&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000502301400001
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85076355897
Appears in Collections:	[Ya-Hui Chi] Periodical Articles

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