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Muscle acetylcholine receptor biosynthesis. Regulation by transcript availability.

S Evans, D Goldman, S Heinemann

    The Journal of Biological Chemistry
    |April 5, 1987
    PubMed
    Summary
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    Muscle nicotinic acetylcholine receptor (AChR) expression is regulated by transcript levels. Changes in AChR subunit transcripts during muscle development and denervation directly impact cell surface receptor appearance.

    Area of Science:

    • Neuroscience
    • Molecular Biology
    • Muscle Physiology

    Background:

    • Muscle nicotinic acetylcholine receptors (AChRs) are crucial for neuromuscular transmission.
    • AChR cell surface expression is dynamic, varying with muscle development and innervation status.

    Purpose of the Study:

    • To investigate the regulatory role of transcript levels on muscle nicotinic acetylcholine receptor (AChR) cell surface expression.
    • To correlate changes in AChR subunit gene transcript abundance with receptor appearance during myogenesis and denervation.

    Main Methods:

    • RNA blot analysis was used to quantify transcript levels of AChR subunits (alpha, beta, gamma, delta).
    • 125I-alpha-bungarotoxin binding assays measured the rate of cell surface AChR appearance in mouse C2 myoblasts.
    • Transcript levels were compared in innervated and denervated rat and mouse skeletal muscle.

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    Main Results:

    • During mouse C2 cell fusion (myogenesis), maximal AChR subunit transcript levels preceded the maximal increase in cell surface AChR.
    • Muscle denervation in rats and mice led to increased transcripts for all four AChR subunits.
    • The beta-subunit transcript showed a distinct pattern, with high levels in innervated rat muscle and a smaller relative increase upon denervation compared to other subunits.

    Conclusions:

    • The availability of AChR subunit transcripts plays a significant regulatory role in the appearance of cell surface receptors.
    • Transcriptional regulation of AChR subunits is a key mechanism controlling receptor levels during muscle development and in response to denervation.