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Published on: December 23, 2010
β-Arrestin 1 mediates non-canonical Wnt pathway to regulate convergent extension movements
Gun-Hwa Kim1, Edmond Changkyun Park, Hyeyoon Lee
1Division of Life Science, Korea Basic Science Institute (KBSI), Daejeon, Republic of Korea.
Abstract:
β-Arrestins are multifaceted proteins that play critical roles in termination of G protein-coupled receptor (GPCR) signaling by inducing its desensitization and internalization as well as in facilitation of many intracellular signaling pathways. Here, we examine using Xenopus embryos whether β-arrestin 1 might act as a mediator of β-catenin-independent Wnt (non-canonical) signaling. Xenopus β-arrestin 1 (xβarr1) is expressed in the tissues undergoing extensive cell rearrangements in early development. Gain- and loss-of-function analyses of xβarr1 revealed that it regulates convergent extension (CE) movements of mesodermal tissue with no effect on cell fate specification. In addition, rescue experiments showed that xβarr1 controls CE movements downstream of Wnt11/Fz7 signal and via activation of RhoA and JNK. In line with this, xβarr1 associated with key Wnt components including Ryk, Fz, and Dishevelled. Furthermore, we found that xβarr1 could recover CE movements inhibited by xβarr2 knockdown or its endocytosis defective mutant. Overall, these results suggest that β-arrestin 1 and 2 share interchangeable endocytic activity to regulate CE movements downstream of the non-canonical Wnt pathway.
Insights
Beta-arrestin 1 mediates non-canonical Wnt signaling in Xenopus embryos, regulating cell movements essential for development. Beta-arrestin 1 and 2 share interchangeable roles in this process.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Beta-arrestins (β-arrestins) are key regulators of G protein-coupled receptor (GPCR) signaling, involved in desensitization and internalization.
- Non-canonical Wnt signaling pathways, independent of β-catenin, are crucial for embryonic development, particularly cell rearrangements.
Purpose of the Study:
- To investigate the role of β-arrestin 1 as a mediator of β-catenin-independent (non-canonical) Wnt signaling.
- To elucidate the function of Xenopus β-arrestin 1 (xβarr1) in early embryonic development, specifically in cell movements.
Main Methods:
- Utilized Xenopus embryos for gain- and loss-of-function analyses of xβarr1.
- Performed rescue experiments to validate the signaling pathway.
- Investigated interactions between xβarr1 and Wnt pathway components (Ryk, Fz, Dishevelled).
Main Results:
- xβarr1 regulates convergent extension (CE) movements in mesodermal tissues without affecting cell fate specification.
- xβarr1 acts downstream of Wnt11/Fz7 signaling and activates RhoA and JNK pathways.
- xβarr1 interacts with Ryk, Fz, and Dishevelled, key components of Wnt signaling.
- xβarr1 and xβarr2 exhibit interchangeable endocytic activity in regulating CE movements.
Conclusions:
- β-arrestin 1 is a critical mediator of non-canonical Wnt signaling, controlling cell rearrangements during embryonic development.
- β-arrestin 1 and β-arrestin 2 possess interchangeable endocytic functions essential for convergent extension movements.
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