IMP/GTP balance modulates cytoophidium assembly and IMPDH activity.
Journal
Cell division
Journal Volume
13
Journal Issue
1
ISSN
1747-1028
Date Issued
2018
Author(s)
Keppeke, Gerson Dierley
Peng, Min
Chen, Li-Yu
Lin, Wei-Cheng
Pai, Li-Mei
Andrade, Luis Eduardo Coelho
Liu, Ji-Long
Abstract
Background: Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in de novo GTP biosynthesis, plays an important role in cell metabolism and proliferation. It has been demonstrated that IMPDH can aggregate into a macrostructure, termed the cytoophidium, in mammalian cells under a variety of conditions. However, the regulation and function of the cytoophidium are still elusive. Results: In this study, we report that spontaneous filamentation of IMPDH is correlated with rapid cell proliferation. Intracellular IMP accumulation promoted cytoophidium assembly, whereas elevated GTP level triggered disassociation of aggregates. By using IMPDH2 CBS domain mutant cell models, which are unable to form the cytoophidium, we have determined that the cytoophidium is of the utmost importance for maintaining the GTP pool and normal cell proliferation in the condition that higher IMPDH activity is required. Conclusions: Together, our results suggest a novel mechanism whereby cytoophidium assembly upregulates IMPDH activity and mediates guanine nucleotide homeostasis.
Subjects
Cell proliferation
Cytoophidium
GTP biosynthesis
IMP
IMPDH enzyme
SDGs
Publisher
Springer Science and Business Media LLC
Description
Article number: 5
Type
journal article