SIL1, the endoplasmic-reticulum-localized BiP co-chaperone, plays a crucial role in maintaining skeletal muscle proteostasis and physiology.

ABSTRACT: Mutations in SIL1, a cofactor for the endoplasmic reticulum (ER)-localized Hsp70 chaperone, BiP, cause Marinesco-Sjögren syndrome (MSS), an autosomal recessive disorder. Using a mouse model, we characterized molecular aspects of the progressive myopathy associated with MSS. Proteomic profiling of quadriceps at the onset of myopathy revealed that SIL1 deficiency affected multiple pathways critical to muscle physiology. We observed an increase in ER chaperones prior to the onset of muscle weakness, which was complemented by upregulation of multiple components of cellular protein degradation pathways. These responses were inadequate to maintain normal expression of secretory pathway proteins, including insulin and IGF-1 receptors. There was a paradoxical enhancement of downstream PI3K-AKT-mTO

SUBMITTER: Ichhaporia VP 

PROVIDER: S-EPMC5992605 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature