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

Rangjuan Cao, Peng Chen, Hongsheng Wang, Hongyang Jing, Hongsheng Zhang, Guanglin Xing, Bin Luo, Jinxiu Pan, Zheng Yu, Wen-Cheng Xiong () and Lin Mei ()
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Rangjuan Cao: Case Western Reserve 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
Lin Mei: Case Western Reserve University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-36454-8

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