Cytoskeletal Regulator Zyxin Stimulates Translocations of YAP into Xenopus laevis Embryo Cell Nuclei

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Abstract

There is limited data in the scientific literature regarding the relationship between mechanotransduction associated with changes in Zyxin levels and biochemical signaling of the transcription factor YAP. Research in this area suggests that stress-induced reorganization of the actin cytoskeleton mediated by Zyxin may play a key role in YAP's mechanotransduction. However, the results of these studies do not provide clear outcomes concerning the effect of Zyxin on YAP distribution between the nucleus and the cytoplasm and its activity regulation. Here, we investigated the effects of Zyxin on the nuclear translocation of the Hippo-signaling pathway effector, YAP, in the early embryo of the clawed frog Xenopus laevis. Analysis of the nuclear-cytoplasmic distribution of YAP by immunoblotting and immunohistochemical staining, combined with the suppression of translation of endogenous Zyxin mRNA by morpholino antisense oligonucleotides and overexpression of synthetic Zyxin mRNA, revealed a stimulatory effect of Zyxin on the nuclear translocation of YAP in gastrula-stage embryos, but not in blastula and neurula stages. A similar conclusion was reached by analyzing the effect of the same changes in Zyxin concentration on the expression of a YAP-dependent luciferase reporter. Based on the results of our study, and taking into account the known role of Zyxin as one of the mechanotransducers, it can be assumed that this protein is involved in the mechano-dependent regulation of the Hippo signaling pathway in embryonic development at the gastrulation stage.

About the authors

E. A Parshina

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Email: lena_parshina5@mail.ru
Moscow, Russia

E. E Orlov

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Moscow, Russia

E. E Voronezhskaya

Koltzov Institute of Developmental Biology of the Russian Academy of Sciences

Moscow, Russia

N. Yu Martynova

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences

Moscow, Russia

A. G Zaraisky

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; Koltzov Institute of Developmental Biology of the Russian Academy of Sciences; Pirogov Russian National Research Medical University

Moscow, Russia; Moscow, Russia; Moscow, Russia

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