Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation.
Journal
Cellular and molecular life sciences : CMLS
Journal Volume
79
Journal Issue
8
ISSN
1420-9071
Date Issued
2022-07-14
Author(s)
Peng, Min
Zhong, Jiale
Zhang, Ziheng
Keppeke, Gerson Dierley
Liu, Ji-Long
Abstract
The cytoophidium is a unique type of membraneless compartment comprising of filamentous protein polymers. Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step of de novo GTP biosynthesis and plays critical roles in active cell metabolism. However, the molecular regulation of cytoophidium formation is poorly understood. Here we show that human IMPDH2 polymers bundle up to form cytoophidium-like aggregates in vitro when macromolecular crowders are present. The self-association of IMPDH polymers is suggested to rely on electrostatic interactions. In cells, the increase of molecular crowding with hyperosmotic medium induces cytoophidia, while the decrease of that by the inhibition of RNA synthesis perturbs cytoophidium assembly. In addition to IMPDH, CTPS and PRPS cytoophidium could be also induced by hyperosmolality, suggesting a universal phenomenon of cytoophidium-forming proteins. Finally, our results indicate that the cytoophidium can prolong the half-life of IMPDH, which is proposed to be one of conserved functions of this subcellular compartment.
Subjects
Cellular compartmentalization
Cytoophidium
IMPDH
Membraneless organelle
Molecular crowding
SDGs
Description
Article number: 420
Type
journal article