mTOR-S6K1 pathway mediates cytoophidium assembly

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Cytosolic CTP synthase (CTPS) forms filamentous structures called cytoophidia, conserved across species.
• The regulation and functional significance of CTPS cytoophidia remain largely unknown.
• Understanding cytoophidium assembly is crucial for deciphering cellular CTP biosynthesis control.

Purpose of the Study:

• To investigate the role of the mechanistic target of rapamycin (mTOR) pathway in regulating CTPS cytoophidium formation.
• To elucidate the specific components of the mTOR pathway involved in this process.
• To establish a link between mTOR signaling and cytoophidium assembly.

Main Methods:

• Utilized mammalian and Drosophila cell culture models.
• Manipulated mTOR pathway activity using inhibitors and genetic knockdown/overexpression.
• Assessed cytoophidium formation via microscopy and quantified changes in filament length and assembly.
• Investigated the involvement of mTORC1 and its downstream target S6K1.

Main Results:

• Inhibition of the mTOR pathway significantly reduced cytoophidium formation in mammalian cells.
• CTPS cytoophidium assembly was primarily dependent on mTOR complex 1 (mTORC1).
• Knockdown of S6K1 inhibited cytoophidium formation, while its constitutive active form rescued mTOR knockdown effects.
• Reduced mTOR expression in Drosophila decreased cytoophidium length in follicle cells.

Conclusions:

• The mechanistic target of rapamycin (mTOR) signaling pathway is a critical regulator of CTPS cytoophidium assembly.
• mTORC1 and its downstream effector S6K1 play key roles in controlling cytoophidium formation.
• This study establishes a novel connection between mTOR signaling and the formation of CTPS cytoophidia.