The Cytoskeletal Protein Zyxin Modulates the Expression of the Target Genes of the Shh Signaling Cascade in the Cells of
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Cytoskeletal Protein Zyxin Modulates the Expression of the Target Genes of the Shh Signaling Cascade in the Cells of the Neural Plate of Embryos of the Spur-Toed Frog Xenopus laevis N. Yu. Martynovaa, 1, E. A. Parshinaa, F. M. Eroshkina, and A. G. Zaraiskya aShemyakin–Ovchinnikov
Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia
Received December 19, 2019; revised December 20, 2019; accepted December 24, 2019
Abstract—It has been shown earlier in a study of the role of the cytoskeletal protein zyxin in cell differentiation in the primordium of the central nervous system (CNS) of the spur-toed frog Xenopus laevis that zyxin interacts with three components of the signaling cascade of the secreted factor Sonic hedgehog (Shh): the transmembrane receptor Patched2 (Ptc2) and the transcription regulators Gli1 and Zic1. In the present work, the effect of zyxin knockdown on the expression of some key proteins of the Shh cascade has been studied. It has been shown using the RT-q PCR that the suppression of zyxin translation enhances the inhibitory effect of Shh on the expression of the target genes of this cascade such as Pax6, Irx3, and Dbx2 and affects the number of transcripts of several genes encoding the proteins that directly provide the functioning of the Shh cascade: Shh, Gli1, Ptc2, and Zic1. A hypothesis has been proposed that zyxin is involved in the regulation of the spatial marking of neural plate cells through the inhibitory effect on the Shh cascade. Keywords: zyxin, sonic hedgehog, signaling pathway, development, Gli1, Zic1 DOI: 10.1134/S1068162020040147
INTRODUCTION Zyxin, a LIM-domain protein, which is predominantly localized in the intracellular part of cell contacts where it regulates the dynamics of the actin cytoskeleton, was first identified in 1991 [1]. In recent years, it has attracted increasing attention owing to its ability to move into the nucleus by the action of mechanical factors and regulate gene expression there [2]. In this connection, it may be suggested that zyxin can modulate the functioning of various signaling cascades that link external effects on the cell with gene expression. This assumption is based on the following data obtained in our laboratory and the data reported in the world literature: —Owing to the localization in the submembrane space, zyxin is capable of interacting with the transmembrane receptors of various ligands and affecting the signal transduction from them into the cell. The possibility of this interaction is supported by the binding of zyxin to the homodimeric transmembrane glycoprotein, the type III receptor for the transforming growth factor β (TGF-β) [3], and the data on the interaction of zyxin with the transmembrane receptor of the Hh factor Patched2 (Ptc2), obtained in our laboratory [4]. 1 Corresponding
author: phone: +7 (916) 181-16-32; fax: +7 (495) 3368611; e-mail: [email protected].
—As shown earlier on a cell culture [5] and in our recent studies on the neural plate cells of Xenopus embryos for the transcript
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