Molecular crowding facilitates bundling of IMPDH polymers and cytoophidium formation
Chang Chia-Chun, Peng Min, Zhong Jiale, Zhang Ziheng, Keppeke Gerson Dierley, Sung Li-Ying, Liu Ji-Long
Journal：CELLULAR AND MOLECULAR LIFE SCIENCES
IF：9.21
DOI：10.1007/s00018-022-04448-2
PMID：35833994
Published：2022-07-14
research field：植物学遗传学分子植物-微生物互作RNA生物学植物病理学
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.
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