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. 2021 Sep 13;9:714330. doi: 10.3389/fcell.2021.714330

FIGURE 4.

FIGURE 4

Regulation of LRP6 maturation and stability. The transmembrane protein LRP6 undergoes several folding and maturation processes to translocate to the plasma membrane and properly function as a Wnt co-receptor. Mesd, USP19, GRP94, and GPR37 promote proper folding of LRP6. Glycosylation and palmitoylation of LRP6 are essential for its maturation. Mest/Peg1 inhibits glycosylation of LRP6 and immature LRP6 is mono-ubiquitinated, resulting in ER retention. Folded and mature LRP6 localizes to the plasma membrane, and CD44 promotes membrane localization of LRP6. ZNRF3 and DVL downregulate LRP6 protein levels, and USP6 and R-spondins antagonize ZNRF3 function. Extracellular stimuli such as hypoxia, ER stress, and starvation also degrade LRP6.