Unconventional SNARE in the ER 1 (Use1) is Expressed in Skeletal Muscle and is Upregulated in Response to Skeletal Muscle Atrophy

Abstract

Muscle atrophy, or a loss in muscle size and strength, results from various physiological conditions and occurs when protein degradation outpaces protein synthesis. Unconventional SNARE in the ER 1 (Use1) protein, in which SNARE stands for soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor, was recently found to be highly upregulated in skeletal muscle cells undergoing atrophy. However, the mechanism of how Use1 is transcriptionally regulated and its potential role in skeletal muscle atrophy is not clear. Interestingly, we have cloned four distinct protein encoding splice‐variants in skeletal muscle, but the significance and functions of these isoforms remains to be determined. It is known that Use1 functions in the endomembrane system (EMS) and that it could play a role in ER stress and the unfolded protein response (UPS) as a consequence of skeletal muscle atrophy. Therefore, in order to simulate atrophy‐induced ER stress in cell culture, we treated cells with Tucamycin (TN) or Thapsigargin (TG) to determine if Use1 expression is impacted in response to UPS activation. If TN or TG induced ER stress results in an increase in Use1 protein, or an isoform switch, it may suggest that Use1 is an important marker of atrophy‐induced ER stress and that it could play an important role in the progression of skeletal muscle wasting. Since muscle atrophy may contribute to increased morbidity and mortality in response to chronic disease states, it is important to gain a better understanding of the factors that participate in the molecular cascade of muscle atrophy, which could lead to the identification of new therapeutic targets for the treatment and prevention of muscle wasting.Support or Funding InformationThe work was support by University of North Florida Transformational Learning Opportunity grants to D.W.