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

Cao, Ruihua; Chen, Peng; Wang, Hongsheng; Jing, Hongyang; Zhang, Hongsheng; Xing, Guanglin; Luo, Bin; Pan, Jin-Xiu; Yu, Zheng; Xiong, Wen-Cheng; Mei, Lin

doi:10.1038/s41467-023-36454-8

Cited by 8 publications

(3 citation statements)

References 113 publications

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“…Muscle spindles comprise intrafusal fibers sensing muscle length alterations and relay these proprioceptive signals to the brain to coordinate movement, posture, and positional awareness. Cao et al 18 studied the role of low-density lipoprotein receptor-related protein 4 (LRP4) in muscle spindle embryonic and postnatal development and aging. The authors created Lrp4 -Cre ERT2 mice with Ai9 reporter to label cells with an active LRP4 promoter.…”

Section: Muscle Physiology and Regenerationmentioning

confidence: 99%

What’s New in Musculoskeletal Basic Science

Gugala

2023

Journal of Bone and Joint Surgery

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Section: Muscle Physiology and Regenerationmentioning

confidence: 99%

What’s New in Musculoskeletal Basic Science

Gugala

2023

Journal of Bone and Joint Surgery

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“…The APP ectodomain can interact with the ligand binding domain of low-density lipoprotein receptor-related protein 4 (LRP4), thereby inducing the phosphorylation of Musk for AChR clustering on its own or cooperatively with agrin [45] (Figure 3). The LRP4 LDLa domain and APP E1 domain are critical sites for their interaction [46]. The ectodomain of APP can also interact with agrin, although which domain that binds to agrin is not well characterized.…”

Section: App's Binding Partners In Nmjmentioning

confidence: 99%

APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer’s Disease

Zou

Lee

et al. 2023

IJMS

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Sarcopenia, an illness condition usually characterized by a loss of skeletal muscle mass and muscle strength or function, is often associated with neurodegenerative diseases, such as Alzheimer’s disease (AD), a common type of dementia, leading to memory loss and other cognitive impairment. However, the underlying mechanisms for their associations and relationships are less well understood. The App, a Mendelian gene for early-onset AD, encodes amyloid precursor protein (APP), a transmembrane protein enriched at both the neuromuscular junction (NMJ) and synapses in the central nervous system (CNS). Here, in this review, we highlight APP and its family members’ physiological functions and Swedish mutant APP (APPswe)’s pathological roles in muscles and NMJ. Understanding APP’s pathophysiological functions in muscles and NMJ is likely to uncover insights not only into neuromuscular diseases but also AD. We summarize key findings from the burgeoning literature, which may open new avenues to investigate the link between muscle cells and brain cells in the development and progression of AD and sarcopenia.

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“…The significance of LRP4 in nervous system function is further highlighted by its association with several human neurodegenerative diseases, including myasthenia gravis (Kalb et al, 2002;Higuchi et al, 2011;Pevzner et al, 2012;Shen et al, 2013;Tsivgoulis et al, 2014;Chung et al, 2023), amyotrophic lateral sclerosis (ALS) (Tzartos et al, 2014) and Alzheimer's disease (Choi et al, 2013;Zhang et al, 2020). In a recent study LRP4 was identified as a novel regulator of muscle spindle formation and maintenance in adult and aged mice (Cao et al, 2023) and LRP4 mediates bone homeostasis and mechanotransduction through interaction with sclerostin (Bullock et al, 2019;Choi and Robling, 2021). In contrast to patients with LRP5-deficiency, who suffer from low bone mass, LRP4 loss-of-function mutations are associated with sclerosteosis 2, characterized by overgrowth of bone mass.…”

mentioning

confidence: 99%

Balancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function

Geng

Paul

Kowalczyk

et al. 2023

Front. Cell Dev. Biol.

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The specification of the forebrain relies on the precise regulation of WNT/ß-catenin signalling to support neuronal progenitor cell expansion, patterning, and morphogenesis. Imbalances in WNT signalling activity in the early neuroepithelium lead to congenital disorders, such as neural tube defects (NTDs). LDL receptor-related protein (LRP) family members, including the well-studied receptors LRP5 and LRP6, play critical roles in modulating WNT signalling capacity through tightly regulated interactions with their co-receptor Frizzled, WNT ligands, inhibitors and intracellular WNT pathway components. However, little is known about the function of LRP4 as a potential modulator of WNT signalling in the central nervous system. In this study, we investigated the role of LRP4 in the regulation of WNT signalling during early mouse forebrain development. Our results demonstrate that LRP4 can modulate LRP5- and LRP6-mediated WNT signalling in the developing forebrain prior to the onset of neurogenesis at embryonic stage 9.5 and is therefore essential for accurate neural tube morphogenesis. Specifically, LRP4 functions as a genetic modifier for impaired mitotic activity and forebrain hypoplasia, but not for NTDs in LRP6-deficient mutants. In vivo and in vitro data provide evidence that LRP4 is a key player in fine-tuning WNT signalling capacity and mitotic activity of mouse neuronal progenitors and of human retinal pigment epithelial (hTERT RPE-1) cells. Our data demonstrate the crucial roles of LRP4 and LRP6 in regulating WNT signalling and forebrain development and highlight the need to consider the interaction between different signalling pathways to understand the underlying mechanisms of disease. The findings have significant implications for our mechanistic understanding of how LRPs participate in controlling WNT signalling.

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

Cited by 8 publications

References 113 publications

What’s New in Musculoskeletal Basic Science

What’s New in Musculoskeletal Basic Science

APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer’s Disease

Balancing WNT signalling in early forebrain development: The role of LRP4 as a modulator of LRP6 function

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