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Seipin Governs caveolin-1 trafficking through modulating sphingolipid-glycerolipid balance
Maxime Carpentier1, Mohyeddine Omrane1, Rola Shaaban2
1Laboratoire de Physique de l'École normale supérieure, ENS, Université PSL, CNRS, Sorbonne Université, Université Paris Cité, Paris F-75005, France.
Seipin deficiency disrupts cellular lipid balance, impairing caveolin-1 (CAV1) transport and caveolae formation. Restoring lipid homeostasis corrects CAV1 localization, revealing seipin
Area of Science:
- Cell Biology
- Lipid Metabolism
- Molecular Trafficking
Background:
- Caveolin-1 (CAV1) is crucial for caveolae formation and cellular function.
- Dysregulation of CAV1 causes various disorders, but its trafficking mechanisms are unclear.
- Seipin is a known regulator of lipid droplet biogenesis.
Purpose of the Study:
- To investigate the role of seipin in regulating caveolin-1 (CAV1) localization and trafficking.
- To elucidate the molecular mechanisms underlying CAV1 transport and caveolae formation.
Main Methods:
- Utilized seipin-deficient mice, HeLa cells, and patient fibroblasts.
- Analyzed lipid composition, membrane order, and protein localization.
- Employed pharmacological interventions targeting lipid synthesis pathways.
Main Results:
- Seipin deficiency led to saturated lipid and ceramide accumulation, disrupting trans-Golgi network (TGN) membrane order.
- Impaired CAV1 trafficking to the plasma membrane, reduced caveolae formation, and CAV1 redirection to lipid droplets (LDs).
- Saturated lipid accumulation was identified as the cause, with interventions restoring CAV1 localization.
Conclusions:
- Seipin regulates lipid fluxes critical for TGN integrity and CAV1 sorting.
- Seipin's role in lipid metabolism directly impacts CAV1 trafficking and caveolae biogenesis.
- Findings offer insights into seipin-mediated cellular lipid homeostasis and its implications for CAV1 function.
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