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Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 21, pp 2508–2515 | Cite as

The nucleotide receptor P2Y13 is a key regulator of hepatic High-Density Lipoprotein (HDL) endocytosis

  • S. Jacquet
  • C. Malaval
  • L. O. Martinez
  • K. Sak
  • C. Rolland
  • C. Perez
  • M. Nauze
  • E. Champagne
  • F. Tercé
  • C. Gachet
  • B. Perret
  • X. Collet
  • J.-M. Boeynaems
  • R. BarbarasEmail author
Research Article

Abstract.

Cell surface receptors for high-density lipoprotein (HDL) on hepatocytes are major partners in the regulation of cholesterol homeostasis. We recently identified a cell surface ATP synthase as a high-affinity receptor for HDL apolipoprotein A-I (apoA-I) on human hepatocytes. Stimulation of this ectopic ATP synthase by apoA-I triggered a low-affinity-receptor-dependent HDL endocytosis by a mechanism strictly related to the generation of ADP. This suggests that nucleotide G-protein- coupled receptors of the P2Y family are molecular components in this pathway. Only P2Y1 and P2Y13 are present on the membrane of hepatocytes. Using both a pharmacological approach and small interference RNA, we identified P2Y13 as the main partner in hepatic HDL endocytosis, in cultured cells as well as in situ in perfused mouse livers. We also found a new important action of the antithrombotic agent AR-C69931MX as a strong activator of P2Y13-mediated HDL endocytosis.

Key words.

HDL lipoprotein receptors nucleotide receptors cholesterol endocytosis 

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Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  • S. Jacquet
    • 1
  • C. Malaval
    • 1
  • L. O. Martinez
    • 1
  • K. Sak
    • 2
    • 3
  • C. Rolland
    • 1
  • C. Perez
    • 1
  • M. Nauze
    • 1
  • E. Champagne
    • 1
  • F. Tercé
    • 1
  • C. Gachet
    • 4
  • B. Perret
    • 1
  • X. Collet
    • 1
  • J.-M. Boeynaems
    • 2
    • 3
  • R. Barbaras
    • 1
    Email author
  1. 1.Dpt. Lipoprotéines et Médiateurs LipidiquesINSERM U563Toulouse, cedex 03France
  2. 2.Institute of Interdisciplinary ResearchFree University of BrusselsBrusselsBelgium
  3. 3.Laboratory of Medical ChemistryErasme HospitalBrusselsBelgium
  4. 4.Unité 311Etablissement Francais du Sang-AlsaceStrasbourg CedexFrance

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