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Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals

Author

Listed:
  • Rangjuan Cao

    (Case Western Reserve University
    China-Japan Union Hospital of Jilin University)

  • Peng Chen

    (Case Western Reserve University)

  • Hongsheng Wang

    (Case Western Reserve University)

  • Hongyang Jing

    (Case Western Reserve University)

  • Hongsheng Zhang

    (Case Western Reserve University)

  • Guanglin Xing

    (Case Western Reserve University)

  • Bin Luo

    (Case Western Reserve University)

  • Jinxiu Pan

    (Case Western Reserve University)

  • Zheng Yu

    (Case Western Reserve University)

  • Wen-Cheng Xiong

    (Case Western Reserve University
    Louis Stokes Cleveland Veterans Affairs Medical Center)

  • Lin Mei

    (Case Western Reserve University
    Louis Stokes Cleveland Veterans Affairs Medical Center)

Abstract

Proprioception is sensed by muscle spindles for precise locomotion and body posture. Unlike the neuromuscular junction (NMJ) for muscle contraction which has been well studied, mechanisms of spindle formation are not well understood. Here we show that sensory nerve terminals are disrupted by the mutation of Lrp4, a gene required for NMJ formation; inducible knockout of Lrp4 in adult mice impairs sensory synapses and movement coordination, suggesting that LRP4 is required for spindle formation and maintenance. LRP4 is critical to the expression of Egr3 during development; in adult mice, it interacts in trans with APP and APLP2 on sensory terminals. Finally, spindle sensory endings and function are impaired in aged mice, deficits that could be diminished by LRP4 expression. These observations uncovered LRP4 as an unexpected regulator of muscle spindle formation and maintenance in adult and aged animals and shed light on potential pathological mechanisms of abnormal muscle proprioception.

Suggested Citation

  • Rangjuan Cao & Peng Chen & Hongsheng Wang & Hongyang Jing & Hongsheng Zhang & Guanglin Xing & Bin Luo & Jinxiu Pan & Zheng Yu & Wen-Cheng Xiong & Lin Mei, 2023. "Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36454-8
    DOI: 10.1038/s41467-023-36454-8
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    References listed on IDEAS

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    1. Minchul Kim & Vedran Franke & Bettina Brandt & Elijah D. Lowenstein & Verena Schöwel & Simone Spuler & Altuna Akalin & Carmen Birchmeier, 2020. "Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Norihiro Yumoto & Natalie Kim & Steven J. Burden, 2012. "Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses," Nature, Nature, vol. 489(7416), pages 438-442, September.
    3. Shing-Hong Lin & Yuan-Ren Cheng & Robert W. Banks & Ming-Yuan Min & Guy S. Bewick & Chih-Cheng Chen, 2016. "Evidence for the involvement of ASIC3 in sensory mechanotransduction in proprioceptors," Nature Communications, Nature, vol. 7(1), pages 1-15, September.
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