| First Author | Wang WP | Year | 2020 |
| Journal | Aging Cell | Volume | 19 |
| Issue | 2 | Pages | e13090 |
| PubMed ID | 31833196 | Mgi Jnum | J:284048 |
| Mgi Id | MGI:6389145 | Doi | 10.1111/acel.13090 |
| Citation | Wang WP, et al. (2020) Progerin in muscle leads to thermogenic and metabolic defects via impaired calcium homeostasis. Aging Cell 19(2):e13090 |
| abstractText | 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 Ca(2+) 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. |
