Do mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption?

Sayali S. Dixit, David E. Sleat, Ann Stock, Peter Lobel

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

NPC1L1 (Niemann-Pick C1-like 1), the pharmacological target of the cholesterol-uptake inhibitor ezetimibe, is a transporter localized on the brush border of enterocytes. Although this protein plays a key role in intestinal uptake of sterols, multiple molecular events that underlie intestinal cholesterol absorption have not been fully characterized. Two proteins that might be involved in this process are NPC1 and NPC2 (Niemann-Pick disease type C proteins 1 and 2), which function in the endosomal/lysosomal cholesterol egress pathway and whose deficiency results in NPC (Niemann-Pick type C) disease. The involvement of these proteins in intestinal cholesterol absorption was examined in mutant mice lacking either NPC1 or NPC2. Our data indicate that deficiencies in either protein do not have an effect on cholesterol uptake or absorption. This contrasts with recent results obtained for the fruitfly Drosophila melanogaster, which indicate that a deficiency of NPC1 (dNPC1a being its Drosophila homologue) leads to activation of an NPC1L1 (Drosophila homologue dNPC1b)-independent cholesterol uptake pathway, underscoring fundamental differences in mammalian and non-mammalian cholesterol metabolism.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalBiochemical Journal
Volume408
Issue number1
DOIs
StatePublished - Nov 15 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Cholesterol transport
  • Ezetimibe
  • Lysosomal protein
  • Niemann-Pick C1-like 1 (NPC1L1)
  • Niemann-Pick type C disease (NPC disease)

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