Djnedd4L Is Required for Head Regeneration by Regulating Stem Cell Maintenance in Planarians.

Qingnan Tian,Jiaxin Li,Yujia Sun,Huimin Fang,Tingting Gao,Shoutao Zhang

doi:10.3390/ijms222111707

Abstract

SUMOylation and ubiquitylation are homologous processes catalyzed by homologous enzymes, and they are involved in nearly all aspects of eukaryotic biology. Planarians, which have the remarkable ability to regenerate their central nervous system (CNS), provide an excellent opportunity to investigate the molecular processes of CNS regeneration in vivo. In this study, we analyzed gene expression profiles during head regeneration with an RNA-seq-based screening approach and found that Djnedd4L and Djubc9 were required for head regeneration in planarians. RNA interference targeting of Djubc9 caused the phospho-H3 mitotic cells to decrease in quantity, or even become absent as a part of the Djubc9 RNAi phenotype, which also showed the collapse of the stem cell lineage along with the reduced expression of epidermal differentiation markers. Furthermore, we found that Djnedd4L RNAi induced increased cell division and promoted the premature differentiation during regeneration. Taken together, our findings show that Djubc9 and Djnedd4L are required for stem cell maintenance in the planarian Dugesia japonica, which helps to elucidate the role of SUMOylation and ubiquitylation in regulating the regeneration process.

Highlights

Protein ubiquitination is a multifaceted posttranslational modification that can lead to protein degradation by the 26S proteasome [1]
Our results suggest that Djubc9 is required for the maintenance of stem cells in planarians and Djnedd4L is required for the reestablishment of anterior domain identities during planarian regeneration
We found that the genes coding ubiquitination and SUMOylation enzymes were differentially expressed genes (DEGs) during head regeneration (Supplementary Material)

Summary

Introduction

Protein ubiquitination is a multifaceted posttranslational modification that can lead to protein degradation by the 26S proteasome [1]. Protein ubiquitination is attached to substrates by a mechanism that involves a number of factors, beginning with an E1 ubiquitin-activating enzyme that makes ubiquitin reactive. Activated ubiquitin is conjugated to an E2 ubiquitin conjugase, which interacts with an E3 ubiquitin ligase to transfer ubiquitin onto a target substrate [2,3,4]. The process of SUMOylation is similar to ubiquitylation, with small ubiquitin-like modifier (SUMO) attaching to substrates through an E1-activating enzyme, an E2-conjugating enzyme, and an E3-ligase [5]. SUMOylation and ubiquitylation regulate various cellular mechanisms, such as protein–protein interactions, protein stability, subcellular localization, cell cycle regulation, and transcription factor activity [4,6,7,8,9]

Methods

Results

Conclusion