LRPs in WNT Signalling

Davidson, Gary

doi:10.1007/164_2021_526

Cited by 22 publications

(13 citation statements)

References 169 publications

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“…As a type I single-pass transmembrane protein, LRP4 easily binds to its ligands and mediates endocytosis ( 25 ), and is necessary for the formation and development of NMJ synapses ( 26 , 27 ). The Agrin–LRP4–MuSK signaling pathway involved and mediated by LRP4 is one of the important mechanisms for inducing AChR cluster aggregation ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis

Zhou

et al. 2022

Front. Immunol.

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Myasthenia gravis (MG) is characterized by autoimmune damage to the postsynaptic membrane of the neuromuscular junction (NMJ) with impaired postsynaptic acetylcholine receptor (AChR) aggregation. Low-density lipoprotein receptor-related protein 4 (LRP4) plays an important role in AChR aggregation at endplate membranes via the Agrin–LRP4–muscle-specific receptor tyrosine kinase (MuSK) cascade. Sorting nexin 17 (SNX17) regulates the degradation and recycling of various internalized membrane proteins. However, whether SNX17 regulates LRP4 remains unclear. Therefore, we examined the regulatory effects of SNX17 on LRP4 and its influence on AChR aggregation in MG. We selected C2C12 myotubes and induced LRP4 internalization via stimulation with anti-LRP4 antibody and confirmed intracellular interaction between SNX17 and LRP4. SNX17 knockdown and overexpression confirmed that SNX17 promoted MuSK phosphorylation and AChR aggregation by increasing cell surface LRP4 expression. By establishing experimental autoimmune MG (EAMG) mouse models, we identified that SNX17 upregulation improved fragmentation of the AChR structure at the NMJ and alleviated leg weakness in EAMG mice. Thus, these results reveal that SNX17 may be a novel target for future MG therapy.

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Section: Discussionmentioning

confidence: 99%

Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis

Zhou

et al. 2022

Front. Immunol.

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“…[158][159][160] Signaling is modulated by coreceptors including LDL related proteins LRP5 (low-density lipoprotein receptor-related protein) and LRP6 and several transmembrane receptor tyrosine kinase-like proteins. 161,162 Wnts are fatty acylated and very hydrophobic, associated with membranes, extracellular vesicles, and lipoprotein particles. 163 The vertebrate genome encodes 19 Wnt ligands and 10 Fzd receptors with downstream signaling relays characterized as either canonical (requiring β-catenin) or noncanonical (calcium/NFAT [nuclear factor of activated T cells], Jun [fos-binding protein p39] kinase, planar cell polarity).…”

Section: Environmental and Modifiable Factors That Accelerate Calcifi...mentioning

confidence: 99%

Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification

Sutton

Malhotra

Hilaire

et al. 2023

ATVB

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Cardiovascular disease is the most common cause of death worldwide, especially beyond the age of 65 years, with the vast majority of morbidity and mortality due to myocardial infarction and stroke. Vascular pathology stems from a combination of genetic risk, environmental factors, and the biologic changes associated with aging. The pathogenesis underlying the development of vascular aging, and vascular calcification with aging, in particular, is still not fully understood. Accumulating data suggests that genetic risk, likely compounded by epigenetic modifications, environmental factors, including diabetes and chronic kidney disease, and the plasticity of vascular smooth muscle cells to acquire an osteogenic phenotype are major determinants of age-associated vascular calcification. Understanding the molecular mechanisms underlying genetic and modifiable risk factors in regulating age-associated vascular pathology may inspire strategies to promote healthy vascular aging. This article summarizes current knowledge of concepts and mechanisms of age-associated vascular disease, with an emphasis on vascular calcification.

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“…The Wnt/β-catenin signaling pathway is highly conserved during evolution and participates in complex interactions with other signaling pathways, such as Notch and BMP signaling, to drive the orderly self-renewal and differentiation of ISCs, ensure crypt cell proliferation and maintain intestinal homeostasis ( Qi et al, 2022 ). Wnt/β-catenin signaling components include Wnt ligands, frizzleds (Fzds), the β-catenin degradation complex, β-catenin, lymphoid enhancer factor/T-cell factor proteins (LEF/TCFs), and various target genes ( Davidson, 2021 ). Wnts in the intestinal stem cell microenvironment are mainly secreted by Paneth and mesenchymal cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

Zheng

Duan

Wen

et al. 2022

Front. Mol. Biosci.

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Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with a complex etiology. Intestinal mucosal injury is an important pathological change in individuals with UC. Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5+) intestinal stem cells (ISCs) exhibit self-renewal and high differentiation potential and play important roles in the repair of intestinal mucosal injury. Moreover, LGR5+ ISCs are intricately regulated by both the Wnt/β-catenin and Notch signaling pathways, which jointly maintain the function of LGR5+ ISCs. Combination therapy targeting multiple signaling pathways and transplantation of LGR5+ ISCs may lead to the development of new clinical therapies for UC.

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LRPs in WNT Signalling

Cited by 22 publications

References 169 publications

Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis

Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis

Molecular Mechanisms of Vascular Health: Insights From Vascular Aging and Calcification

Molecular regulation after mucosal injury and regeneration in ulcerative colitis

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