CTPS and IMPDH form cytoophidia in developmental thymocytes

Area of Science:

• Cell Biology
• Biochemistry
• Immunology

Background:

• Cytoophidia are filamentous structures formed by metabolic enzymes, acting as novel regulatory machinery.
• Cytidine triphosphate synthase (CTPS) and inosine monophosphate dehydrogenase (IMPDH) are key cytoophidium-forming enzymes.
• CTPS cytoophidia presence in normal mammalian tissues is largely uncharacterized.

Purpose of the Study:

• To investigate the presence and physiological role of CTPS cytoophidia in normal mammalian tissues.
• To explore the association between cytoophidia formation, cell metabolism, and thymocyte development.

Main Methods:

• Systemic survey of CTPS cytoophidia in major adult mouse organs.
• Analysis of thymocyte populations (DN3 to early DP stages) for cytoophidia.
• Assessment of metabolic markers (c-Myc, phospho-Akt, PFK) and glycolytic inhibition (2DG).

Main Results:

• CTPS cytoophidia are present in a specific thymocyte population (DN3 to early DP stages) undergoing rapid proliferation.
• These cells co-express both CTPS and IMPDH cytoophidia and exhibit heightened glycolytic metabolism.
• Inhibition of glycolysis disrupts cytoophidia and impairs cell proliferation.

Conclusions:

• CTPS and IMPDH cytoophidia formation is linked to metabolic shifts triggered by pre-TCR signaling during thymocyte development.
• Cytoophidia likely play a physiological role in thymocyte development and proliferation.