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

Abstract

beta-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 beta-arrestin 1 might act as a mediator of beta-catenin-independent Wnt (non-canonical) signaling. Xenopus beta-arrestin 1 (x beta arr1) is expressed in the tissues undergoing extensive cell rearrangements in early development. Gain- and loss-of-function analyses of x beta arr1 revealed that it regulates convergent extension (CE) movements of mesodermal tissue with no effect on cell fate specification. In addition, rescue experiments showed that x beta arr1 controls CE movements downstream of Wnt11/Fz7 signal and via activation of RhoA and JNK. In line with this, x beta arr1 associated with key Wnt components including Ryk, Fz, and Dishevelled. Furthermore, we found that x beta arr1 could recover CE movements inhibited by x beta arr2 knockdown or its endocytosis defective mutant. Overall, these results suggest that beta-arrestin 1 and 2 share interchangeable endocytic activity to regulate CE movements downstream of the non-canonical Wnt pathway. (c) 2013 Elsevier Inc. All rights reserved.