Limiting role of protein disulfide isomerase in the expression of collagen-tailed acetylcholinesterase forms in muscle

Carlos A. Ruiz, Richard L Rotundo

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The expression of acetylcholinesterase (AChE) in skeletal muscle is regulated by muscle activity; however, the underlying molecular mechanisms are incompletely understood. We show here that the expression of the synaptic collagen-tailed AChE form (ColQ-AChE) in quail muscle cultures can be regulated by muscle activity post-translationally. Inhibition of thiol oxidoreductase activity decreases expression of all active AChE forms. Likewise, primary quail myotubes transfected with protein disulfide isomerase (PDI) short hairpin RNAs showed a significant decrease of both the intracellular pool of all collagen-tailed AChE forms and cell surface AChE clusters. Conversely, overexpression of PDI, endoplasmic reticulum protein 72, or calnexin in muscle cells enhanced expression of all collagen-tailed AChE forms. Overexpression of PDI had the most dramatic effect with a 100% increase in the intracellular ColQ-AChE pool and cell surface enzyme activity. Moreover, the levels of PDI are regulated by muscle activity and correlate with the levels of ColQ-AChE and AChE tetramers. Finally, we demonstrate that PDI interacts directly with AChE intracellularly. These results show that collagen-tailed AChE form levels induced by muscle activity can be regulated by molecular chaperones and suggest that newly synthesized exportable proteins may compete for chaperone assistance during the folding process.

Original languageEnglish
Pages (from-to)31753-31763
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number46
DOIs
StatePublished - Nov 30 2009

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Protein Disulfide-Isomerases
Acetylcholinesterase
Muscle
Collagen
Muscles
Quail
Calnexin
Molecular Chaperones
Skeletal Muscle Fibers
Enzyme activity
Sulfhydryl Compounds
Endoplasmic Reticulum
Muscle Cells
Small Interfering RNA
Oxidoreductases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Limiting role of protein disulfide isomerase in the expression of collagen-tailed acetylcholinesterase forms in muscle. / Ruiz, Carlos A.; Rotundo, Richard L.

In: Journal of Biological Chemistry, Vol. 284, No. 46, 30.11.2009, p. 31753-31763.

Research output: Contribution to journalArticle

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