ß-Arrestin 1 mediates non-canonical Wnt pathway to regulate convergent extension movements.

ABSTRACT

ß-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 ß-arrestin 1 might act as a mediator of ß-catenin-independent Wnt (non-canonical) signaling. Xenopus ß-arrestin 1 (xßarr1) is expressed in the tissues undergoing extensive cell rearrangements in early development. Gain- and loss-of-function analyses of xßarr1 revealed that it regulates convergent extension (CE) movements of mesodermal tissue with no effect on cell fate specification. In addition, rescue experiments showed that xßarr1 controls CE movements downstream of Wnt11/Fz7 signal and via activation of RhoA and JNK. In line with this, xßarr1 associated with key Wnt components including Ryk, Fz, and Dishevelled. Furthermore, we found that xßarr1 could recover CE movements inhibited by xßarr2 knockdown or its endocytosis defective mutant. Overall, these results suggest that ß-arrestin 1 and 2 share interchangeable endocytic activity to regulate CE movements downstream of the non-canonical Wnt pathway.