ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
ABSTRACTS â ORAL PRESENTATIONS - AMCA, spol. s r.o.
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Fam123b. Amer1 has been shown very recently to bridge Wnt-induced and Dishevelled<br />
(Dvl)-associated PtdIns(4,5)P 2<br />
production to the phosphorylation of Lrp6 (Tanenberger<br />
K, et al., 2011). We show here that β-arrestin is required for the Wnt3a-induced Amer1<br />
membrane dynamics (Fig.1) and downstream signaling. Finally we show that β-arrestin<br />
interaction with PtdIns kinases is responsible for Wnt3a-induced PtdIns(4,5)P 2<br />
formation<br />
(PI4KIIα and PIP5KIβ). Importantly, cells lacking β-arrestin showed higher steady state<br />
levels of relevant PtdInsP and were unable to increase levels of these PtdInsP in response<br />
to Wnt3a. In summary, our data show that β-arrestins regulate Wnt3a-induced Lrp6<br />
phosphorylation by the regulation of the membrane dynamics of Amer1. We propose<br />
that β-arrestins via their scaffolding function facilitate Amer1 interaction with PtdIns(4,5)<br />
P 2<br />
, which is produced locally upon Wnt3a stimulation by β-arrestin- and Dvl-associated<br />
kinases.<br />
Figure 1. Wnt3a is unable to regulate AMER1 dynamics in the absence of β-arrestin<br />
and in the case of AMER1(2-838aa) construct, which lacks the β-arrestin interaction<br />
domain.<br />
Acknowledgements<br />
This work was supported by Czech Science Foundation (204/09/0498, 204/09/J030),<br />
EMBO Installation Grant, the Ministry of Education Youth and Sport of the Czech<br />
Republic (MSM0021622430). GS is supported by Knut and Alice Wallenberg Foundation<br />
(KAW2008.0149), Swedish Research Council (K2008-68P-20810-01-4, K2008-<br />
68K-20805-01-4) and The Swedish Foundation for International Cooperation in Research<br />
and Higher Education (STINT). JB is supported by grant Be1550/6-1 from Deutsche<br />
Forschungsgemeinschaft (DFG). The collaboration between Masaryk University and<br />
Karolinska Institutet is supported by by the European Regional Development Fund (KI-<br />
MU; CZ.1.07/2.3.00/20.0180).<br />
References<br />
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of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science<br />
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2. Schulte, G., A. Schambony, and V. Bryja. 2010. beta-Arrestins - scaffolds and signalling<br />
elements essential for WNT/Frizzled signalling pathways? Br J Pharmacol 159:1051-1058.<br />
3. Tanneberger, K., A. S. Pfister, K. Brauburger, J. Schneikert, M. V. Hadjihannas, V. Kriz, G.<br />
Schulte, V. Bryja, and J. Behrens. 2011. Amer1/WTX couples Wnt-induced formation of<br />
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Legend to figure<br />
Fig. 1: Analysis of AMER1 membrane dynamics in presence and absence of β-arrestin<br />
116 Analytical Cytometry VII
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