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Review
. 2021 May 6:9:670960.
doi: 10.3389/fcell.2021.670960. eCollection 2021.

LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence

Qian Ren  1 , Jiongcheng Chen  1 , Youhua Liu  1   2
Affiliations
Review

LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence

Qian Ren et al. Front Cell Dev Biol. .

Abstract

The canonical Wnt/β-catenin signaling plays a fundamental role in regulating embryonic development, injury repair and the pathogenesis of human diseases. In vertebrates, low density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), the single-pass transmembrane proteins, act as coreceptors of Wnt ligands and are indispensable for Wnt signal transduction. LRP5 and LRP6 are highly homologous and widely co-expressed in embryonic and adult tissues, and they share similar function in mediating Wnt signaling. However, they also exhibit distinct characteristics by interacting with different protein partners. As such, each of them possesses its own unique functions. In this review, we systematically discuss the similarity and divergence of LRP5 and LRP6 in mediating Wnt and other signaling in the context of kidney diseases. A better understanding of the precise role of LRP5 and LRP6 may afford us to identify and refine therapeutic targets for the treatment of a variety of human diseases.

Keywords: LRP5; LRP6; Wnt; YAP; chronic kidney disease; kidney fibrosis; β-catenin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Structural similarity of human LRP5 and LRP6 proteins. The schematic diagram shows the structure of human LRP6 and LRP5 with different colors representing various domains. The numbers listed at the top of the domain represent the boundaries of signal peptides and four EGF-like domains in the full-length protein. The numbers at the bottom shows the amino acid identity between human LRP6 and LRP5. The binding sites of LRP5/6 to different Wnt ligands are indicated. ECD, extracellular domain; TM, transmembrane domain; ICD, intracellular domain.
FIGURE 2
FIGURE 2
The distinct role of LRP5 and LRP6 in mediating Wnt/β-catenin and YAP/TAZ signaling. Both LRP5 and LRP6, as co-receptors of Wnt ligands, mediate Wnt/β-catenin signaling. However, when Wnt binds to and activates LRP6, activated LRP6, but not LRP5, also competitively binds to the same domain of Axin that is responsible for binding with YAP/TAZ. As a result, this leads to the release of YAP/TAZ from the destruction complex, resulting in their accumulation in the cytoplasm and translocation into the nucleus, where they bind to their cognate transcription factor TEAD and mediate the expression of their target genes.
See this image and copyright information in PMC

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