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Control of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function

Author

Listed:
  • Ina Klockner

    (Max Planck Institute for Heart- and Lung Research, Department of Cardiac Development and Remodelling)

  • Christian Schutt

    (Max Planck Institute for Heart- and Lung Research, Department of Cardiac Development and Remodelling)

  • Theresa Gerhardt

    (Max Planck Institute for Heart- and Lung Research, Department of Cardiac Development and Remodelling)

  • Thomas Boettger

    (Max Planck Institute for Heart- and Lung Research, Department of Cardiac Development and Remodelling)

  • Thomas Braun

    (Max Planck Institute for Heart- and Lung Research, Department of Cardiac Development and Remodelling)

Abstract

Formation and maintenance of neuromuscular junctions (NMJs) are essential for skeletal muscle function, allowing voluntary movements and maintenance of the muscle tone, thereby preventing atrophy. Generation of NMJs depends on the interaction of motor neurons with skeletal muscle fibers, which initiates a cascade of regulatory events that is essential for patterning of acetylcholine receptor (AChR) clusters at specific sites of the sarcolemma. Here, we show that muscle-specific miRNAs of the miR-1/206/133 family are crucial regulators of a signaling cascade comprising DOK7-CRK-RAC1, which is critical for stabilization and anchoring of postsynaptic AChRs during NMJ development and maintenance. We describe that posttranscriptional repression of CRK by miR-1/206/133 is essential for balanced activation of RAC1. Failure to adjust RAC1 activity severely compromises NMJ function, causing respiratory failure in neonates and neuromuscular symptoms in adult mice. We conclude that miR-1/206/133 serve a specific function for NMJs but are dispensable for skeletal muscle development.

Suggested Citation

  • Ina Klockner & Christian Schutt & Theresa Gerhardt & Thomas Boettger & Thomas Braun, 2022. "Control of CRK-RAC1 activity by the miR-1/206/133 miRNA family is essential for neuromuscular junction function," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30778-7
    DOI: 10.1038/s41467-022-30778-7
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    References listed on IDEAS

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    1. Weichun Lin & Robert W. Burgess & Bertha Dominguez & Samuel L. Pfaff & Joshua R. Sanes & Kuo-Fen Lee, 2001. "Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse," Nature, Nature, vol. 410(6832), pages 1057-1064, April.
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