Interfilament interaction between IMPDH and CTPS cytoophidia

Abstract

Inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthase (CTPS) are two metabolic enzymes that perform rate‐limiting steps in the de novo synthesis of purine and pyrimidine nucleotides, respectively. It has been shown that IMPDH and CTPS can comprise a filamentous macrostructure termed the cytoophidium, which may play a role in regulation of their catalytic activity. Although these two proteins may colocalise in the same cytoophidium, how they associate with one another is still elusive. As reported herein, we established a model HeLa cell line coexpressing OFP‐tagged IMPDH2 and GFP‐tagged CTPS1 and recorded the assembly, disassembly and movement of the cytoophidium in live cells. Moreover, by using super‐resolution confocal imaging, we demonstrate how IMPDH‐ and CTPS‐based filaments are aligned or intertwined in the mixed cytoophidium. Collectively, our findings provide a panorama of cytoophidium dynamics and suggest that IMPDH and CTPS cytoophidia may coordinate by interfilament interaction.

Filamentation of asparagine synthetase in Saccharomyces cerevisiae

“…Further studies are required to understand the dynamic interaction and functional connection, if any, between ASNS and CTPS cytoophidia. Previous studies have shown that CTPS cytoophidia have interfilament interaction with inosine monophosphate dehydrogenase (IMPDH) cytoophidia [ 21 , 22 ], suggesting that the interaction between two cytoophidia may be a phenomenon more general than we have appreciated.…”

“…Does the ASNS cytoophidium have similar functions of the CTPS cytoophidium? Since there are quite a few metabolic enzymes showing the filament-forming capability, we speculate that cytoophidia have more general functions in the cell [ 21 , 22 ]. The close proximity between ASNS and CTPS cytoophidia raises the possibility that both enzymes function coordinately in maintaining metabolic homeostasis in the cytoplasm and nucleus.…”

The value of anti‐rods and rings antibodies in Western China population: A retrospective study

“…4,5 Although the exact components of RR are still not very clear, inosine monophosphate dehydrogenase type 2 (IMPDH2) and cytidine triphosphate synthase 1 (CTPS1) are definitely the components of RR. 6 It is reported that IMPDH2 can catalyse the conversion of inosine monophosphate into xanthosine monophosphate in the GTP biosynthesis pathway and CTPS1 can catalyse the conversion of uridine triphosphate into cytidine triphosphate. Altogether, RR is considered to be the key point in nucleic acid and phospholipid biosynthesis.…”

Anfractuous assemblies of IMP dehydrogenase and CTP synthase: new twists on regulation?

“…1) [12]. In this issue of The FEBS Journal, Liu, Sung, and co-workers [14] explore the morphology and dynamics of CTPS1/IMPDH2-containing assemblies in live human cells. IMPDH catalyses the (NAD + )-dependent oxidation of IMP to xanthosine-5 0 -monophosphate, which is the rate-limiting step in the de novo biosynthesis of guanine nucleotides [13].…”

“…Because rapidly proliferating cells require CTP and GTP, both allosterically controlled enzymes are targets for the development of anticancer, antiviral, and immunosuppressive chemotherapies. In this issue of The FEBS Journal, Liu, Sung, and co-workers [14] explore the morphology and dynamics of CTPS1/IMPDH2-containing assemblies in live human cells.…”