The LDL receptor-related protein 6 (LRP6) was first identified as a Wnt co-receptor in mice. However, the precise role that LRP6 plays in Wnt signalling has remained unclear. On p. 503, Janet Heasman's group now reveal that LRP6 degrades axin - an essential event in the Wnt11-activated formation of the dorsal axis in Xenopusembryogenesis. They also reveal that LRP6 regulates axin levels in the oocyte and maintains β-catenin expression in a low steady state - Wnt signalling has previously been believed to exist in either an on or off state. Axin is a negative regulator of Wnt signalling that targets β-catenin for degradation, so preventing Wnt target gene activation. LRP6 depletion in the embryo, in this study, led to increased axin and decreased β-catenin levels. In wild-type oocytes, exogenous β-catenin degradation was prevented by the co-injection of LRP6 mRNA, whereas in axin-depleted oocytes, β-catenin levels increased. This study reveals a novel role for LRP6 in axin degradation and highlights the complexity of Wnt signalling.
LRP6: axing axin
LRP6: axing axin. Development 1 February 2007; 134 (3): e303. doi:
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