Essential role for beta-arrestin 2 in the regulation of Xenopus convergent extension movements

Abstract

beta-Arrestin 2 (beta arr2) is a multifunctional protein that regulates numerous aspects of G-protein-coupled receptor function. However, its possible involvement in developmental processes is poorly understood. In this work, we examined the potential role of beta arr2 during Xenopus early development. Gain-and loss-of-function studies showed that Xenopus beta arr2 (x beta arr2) is required for proper convergent extension (CE) movements, and normal cell polarization and intercalation without affecting cell fate. Moreover, for CE movements, beta arr2 acts as an essential regulator of dishevelled-mediated PCP (planar cell polarity) signaling, but not G-protein-mediated Ca2+ signaling. Notably, xbarr2 is localized with the same distribution as the dishevelled protein, which is reasonable, as x beta arr2 is required for dishevelled activation of RhoA. Furthermore, x beta arr2 interacts with the N-terminal quarter of Daam1 and RhoA proteins, but not Rac1, and regulates RhoA activation through Daam1 activation for CE movements. We provide evidence that the endocytic activity of x beta arr2 is essential for control of CE movements. Taken together, our results suggest that beta arr2 has a pivotal role in the regulation of Xenopus CE movements.