A maladaptive ER stress response triggers dysfunction in highly active muscles of mice with SELENON loss.

ABSTRACT: Selenoprotein N (SELENON) is an endoplasmic reticulum (ER) protein whose loss of function leads to human SELENON-related myopathies. SelenoN knockout (KO) mouse limb muscles, however, are protected from the disease, and display no major alterations in muscle histology or contractile properties. Interestingly, we find that the highly active diaphragm muscle shows impaired force production, in line with the human phenotype. In addition, after repeated stimulation with a protocol which induces muscle fatigue, also hind limb muscles show altered relaxation times. Mechanistically, muscle SELENON loss alters activity-dependent calcium handling selectively impinging on the Ca²⁺ uptake of the sarcoplasmic reticulum and elicits an ER stress response, including the expression of the malad

SUBMITTER: Pozzer D 

PROVIDER: S-EPMC6223234 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature