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Proteasome function is required to maintain muscle cellular architecture
Author(s) -
Haas Kevin F.,
Woodruff Elvin,
Broadie Kendal
Publication year - 2007
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1042/bc20070019
Subject(s) - biology , proteasome , endoplasmic reticulum , microbiology and biotechnology , muscle atrophy , sarcomere , protein degradation , neuromuscular junction , autophagy , ubiquitin , myocyte , skeletal muscle , biochemistry , anatomy , neuroscience , apoptosis , gene
Background information . Protein degradation via the UPS (ubiquitin—proteasome system) plays critical roles in muscle metabolism and signalling pathways. The present study investigates temporal requirements of the UPS in muscle using conditional expression of mutant proteasome β subunits to cause targeted inhibition of proteasome function. Results and conclusions . The Drosophila GeneSwitch system was used, with analyses of the well‐characterized larval somatic body wall muscles. This method acutely disrupts proteasome function and causes rapid accumulation of polyubiquitinated proteins, specifically within the muscle. Within 12 h of transgenic proteasome inhibition, there was a gross disorganization of muscle architecture and prominent muscle atrophy, progressing to the arrest of all co‐ordinated movement by 24 h. Progressive muscle architecture changes include rapid loss of sarcomere organization, loss of nuclei spacing/patterning, vacuole formation and the accumulation of nuclear and cytoplasmic aggregates at the ultrastructural level. At the neuromuscular junction, the highly specialized muscle membrane folds of the subsynaptic reticulum were rapidly lost. Within 24 h after transgenic proteasome inhibition, muscles contained numerous autophagosomes and displayed highly elevated expression of the endoplasmic reticulum chaperone GRP78 (glucose‐regulated protein of 78 kDa), indicating that the loss of muscle maintenance correlates with induction of the unfolded protein response. Taken together, these results demonstrate that the UPS is acutely required for maintenance of muscle and neuromuscular junction architecture, and provides a Drosophila genetic model to mechanistically evaluate this requirement.