Related Experiment Video

Updated: May 22, 2026

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
08:49

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes

Published on: March 14, 2021

The mTOR-Dop1a-Agpat2 axis regulates nuclear phospholipid homeostasis

Hirotaka Ariyama1, Atsushi Tsukamura2, Satoko Miyatake3,4,5

  • 1Department of Pediatric Physiology, Innovation & Research Support Center, Graduate School, International University of Health and Welfare, Tokyo, Japan.

Iscience
|May 21, 2026
PubMed

Insights

Dop1a protein regulates nuclear phospholipid synthesis, preventing lipid droplet formation and ensuring proper cell division. Its dysfunction is linked to neurodevelopmental disorders.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Nuclear phospholipid metabolism is poorly understood.
  • Dop1a's role in nuclear lipid homeostasis is unknown.
  • mTOR signaling influences nuclear lipid metabolism.

Purpose of the Study:

  • To elucidate the function of Dop1a in regulating nuclear phospholipid metabolism.
  • To investigate the link between Dop1a, mTOR signaling, and nuclear lipid synthesis.
  • To determine the role of Dop1a in cell cycle regulation and neurodevelopment.

Main Methods:

  • Investigated Dop1a localization and binding partners (AGPAT2) at nuclear pore complexes.
  • Analyzed phospholipid levels and nuclear lipid droplet formation in wild-type and Dop1a-deficient cells.
  • Assessed the impact of Dop1a on cell cycle progression and CDK2 nuclear accumulation.
  • Examined Dop1a expression in neurons and the consequences of its mutations in neurodevelopmental disorders.

Main Results:

  • Dop1a localizes to nuclear pore complexes upon lysophosphatidic acid shortage, suppressing phospholipid synthesis by inhibiting AGPAT2.
  • Loss of Dop1a leads to increased phospholipid production and nuclear lipid droplet formation.
  • Dop1a restricts CDK2 nuclear accumulation, coordinating phospholipid levels with cell cycle entry.
  • Dop1a is crucial for neurobehavioral development, and its mutations are associated with neurodevelopmental disorders.

Conclusions:

  • Dop1a acts as a key regulator of nuclear phospholipid homeostasis, safeguarding cell division.
  • Dop1a's function is essential for proper nervous system development.
  • Dysregulation of Dop1a is implicated in neurodevelopmental disorders, highlighting its clinical relevance.
Keywords:
biological sciences

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