?-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein
Kriz V, Pospichalova V, Masek J, Kilander MBC, Slavik J, Tanneberger K, Schulte G, Machala M, Kozubik A, Behrens J, Bryja V (2014)
Publication Type: Journal article
Publication year: 2014
Journal
Publisher: American Society for Biochemistry and Molecular Biology
Book Volume: 289
Pages Range: 1128-41
Journal Issue: 2
Abstract
?-Arrestin is a scaffold protein that regulates signal transduction by seven transmembrane-spanning receptors. Among other functions it is also critically required for Wnt/?-catenin signal transduction. In the present study we provide for the first time a mechanistic basis for the ?-arrestin function in Wnt/?-catenin signaling. We demonstrate that ?-arrestin is required for efficient Wnt3a-induced Lrp6 phosphorylation, a key event in downstream signaling. ?-Arrestin regulates Lrp6 phosphorylation via a novel interaction with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-binding protein Amer1/WTX/Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled-associated PtdIns(4,5)P2 production to the phosphorylation of Lrp6. Using fluorescence recovery after photobleaching we show here that ?-arrestin is required for the Wnt3a-induced Amer1 membrane dynamics and downstream signaling. Finally, we show that ?-arrestin interacts with PtdIns kinases PI4KII? and PIP5KI?. Importantly, cells lacking ?-arrestin showed higher steady-state levels of the relevant PtdInsP and were unable to increase levels of these PtdInsP in response to Wnt3a. In summary, our data show that ?-arrestins regulate Wnt3a-induced Lrp6 phosphorylation by the regulation of the membrane dynamics of Amer1. We propose that ?-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)P2, which is produced locally upon Wnt3a stimulation by ?-arrestin- and Dishevelled-associated kinases.
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APA:
Kriz, V., Pospichalova, V., Masek, J., Kilander, M.B.C., Slavik, J., Tanneberger, K.,... Bryja, V. (2014). ?-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein. Journal of Biological Chemistry, 289(2), 1128-41. https://doi.org/10.1074/jbc.M113.498444
MLA:
Kriz, Vitezslav, et al. "?-Arrestin Promotes Wnt-induced Low Density Lipoprotein Receptor-related Protein 6 (Lrp6) Phosphorylation via Increased Membrane Recruitment of Amer1 Protein." Journal of Biological Chemistry 289.2 (2014): 1128-41.
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