Functional interactions between anthrax toxin receptors and the WNT signalling protein LRP6
Article first published online: 20 AUG 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Volume 10, Issue 12, pages 2509–2519, December 2008
How to Cite
Abrami, L., Kunz, B., Deuquet, J., Bafico, A., Davidson, G. and Van Der Goot, F. G. (2008), Functional interactions between anthrax toxin receptors and the WNT signalling protein LRP6. Cellular Microbiology, 10: 2509–2519. doi: 10.1111/j.1462-5822.2008.01226.x
- Issue published online: 6 NOV 2008
- Article first published online: 20 AUG 2008
- Received 26 May, 2008; revised 25 July, 2008; accepted 30 July, 2008.
To exert its activity, anthrax toxin must be endocytosed and its enzymatic toxic subunits delivered to the cytoplasm. It has been proposed that, in addition to the anthrax toxin receptors (ATRs), lipoprotein-receptor-related protein 6 (LRP6), known for its role in Wnt signalling, is also required for toxin endocytosis. These findings have however been challenged. We show that LRP6 can indeed form a complex with ATRs, and that this interaction plays a role both in Wnt signalling and in anthrax toxin endocytosis. We found that ATRs control the levels of LRP6 in cells, and thus the Wnt signalling capacity. RNAi against ATRs indeed led to a drastic decrease in LRP6 levels and a subsequent drop in Wnt signalling. Conversely, LRP6 plays a role in anthrax toxin endocytosis, but is not essential. We indeed found that toxin binding triggered tyrosine phosphorylation of LRP6, induced its redistribution into detergent-resistant domains, and its subsequent endocytosis. RNAis against LRP6 strongly delayed toxin endocytosis. As the physiological role of ATRs is probably to interact with the extracellular matrix, our findings raise the interesting possibility that, through the ATR–LRP6 interaction, adhesion to the extracellular matrix could locally control Wnt signalling.