Reactome | RSPO:LGR binds ZNRF3

RSPO:LGR binds ZNRF3

Stable Identifier

R-HSA-4641205

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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RSPO1-4 increase the levels of FZD and LRP6 receptors and decrease the amount of ZNRF3 at the plasma membrane. RSPO-induced internalization of ZNRF3 depends on LGR and the ubiquitin ligase activity of ZNRF3, and RSPO has been shown to bind directly to the extracellular region of ZNRF3 in an LGR-independent manner. These data are consistent with a model where RSPO promotes an interaction between ZNRF3 and LGR proteins that is required for downregulation of the ubiquitin ligase. In support of this model, artificial dimerization of ZNRF3 and LGR bypasses the requirement for RSPO in ZNRF3 internalization (Hao et al, 2012).

Literature References

PubMed ID	Title	Journal	Year
22575959	ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner Mickanin, C, Zhang, Y, Bouwmeester, T, Zamponi, R, Xie, Y, Liu, D, Charlat, O, Kirschner, MW, Cong, F, Porter, JA, Avello, M, Lei, H, Serluca, FC, Finan, PM, Oster, E, Hao, HX, Ma, Q, Ruffner, H, Mao, X	Nature	2012