Tubular aggregates are from whole sarcoplasmic reticulum origin: alterations in calcium binding protein expression in mouse skeletal muscle during aging

Abstract

Tubular aggregates are observed in various muscle disorders and appear as densely packed tubules believed to arise from sarcoplasmic reticulum of striated muscle. They are found both in human skeletal muscle, especially from patients suffering from 'tubular aggregate myopathy' and in fast twitch skeletal muscle of the male inbred mouse during aging. In this work, we studied tubular aggregates present in inbred male mouse skeletal muscle using electron microscopy as well as histochemistry and Western blotting with the main markers of the sarcoplasmic reticulum. We show that mouse tubular aggregates include the proteins SERCA 1, sarcalumenin (longitudinal sarcoplasmic reticulum), calsequestrin (terminal cisternae) and RyR1 (junctional sarcoplasmic reticulum). We demonstrate also that 95 and 51 kDa triadin isoforms are present in mouse skeletal muscle and are both components of tubular aggregates. These results support the hypothesis that tubular aggregates form a tubular arrangement of a complete sarcoplasmic reticulum containing the junctional, cisternae and longitudinal components of sarcoplasmic reticulum implicated in calcium homeostasis. During mouse skeletal muscle aging, however, densitometry of Western blots reveals a persistent decrease in the expression of the calcium binding protein calreticulin as well as a continuous increase in calsequestrin-like protein expression which both appear unrelated to the tubular aggregate formation.