Biochem. J. (2007) 408
(e1–e3) (Printed in Great Britain)
Commentary
A role for NPC1 and NPC2 in intestinal cholesterol absorption – the hypothesis gutted
Laura LISCUM1
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111, U.S.A.
Dietary and biliary cholesterol are taken up by intestinal epithelial cells and transported to the endoplasmic reticulum. At the endoplasmic reticulum, cholesterol is esterified, packaged into chylomicrons and secreted into the lymph for delivery to the bloodstream. NPC1L1 (Niemann–Pick C1-like 1) is a protein on the enterocyte brush-border membrane that facilitates cholesterol absorption. Cholesterol's itinerary as it moves to the endoplasmic reticulum is unknown, as is the identity of any cellular proteins that facilitate the movement. Two proteins that play an important role in intracellular cholesterol transport and could potentially influence NPC1L1-mediated cholesterol uptake are NPC1 and NPC2 (Niemann–Pick type C disease proteins 1 and 2). In this issue of the Biochemical Journal, Dixit and colleagues show that the absence or presence of NPC1 and NPC2 has no effect on intestinal cholesterol absorption in the mouse. Thus neither protein fills the gap in our knowledge of intra-enterocyte cholesterol transport. Furthermore, the NPC1/NPC2 pathway would not be a good target for limiting the uptake of dietary cholesterol.
Key words: absorption, cholesterol transport, Niemann–Pick C1-like 1 (NPC1L1), Niemann–Pick type C disease (NPC), Niemann–Pick type C disease proteins 1 and 2 (NPC1 and NPC2).
1email laura.liscum@tufts.edu
Received 28 September 2007; accepted 1 October 2007
Published on the Internet 29 October 2007, doi:10.1042/BJ20071340
© The Authors Journal compilation © 2007 Biochemical Society
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