Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport
نویسندگان
چکیده
منابع مشابه
Genetic evidence for nonredundant functional cooperativity between NPC1 and NPC2 in lipid transport.
Niemann-Pick C (NPC) disease is a fatal neurodegenerative disorder characterized by a lysosomal accumulation of cholesterol and other lipids within the cells of patients. Clinically identical forms of NPC disease are caused by defects in either of two different proteins: NPC1, a lysosomal-endosomal transmembrane protein and NPC2, a soluble lysosomal protein with cholesterol binding properties. ...
متن کاملNPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes.
Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann-Pick C1 (NPC1) and soluble Niemann-Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25-264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed ...
متن کاملA role for NPC1 and NPC2 in intestinal cholesterol absorption--the hypothesis gutted.
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. Chol...
متن کاملDo mammalian NPC1 and NPC2 play a role in intestinal cholesterol absorption?
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 pr...
متن کاملConsequences of NPC1 and NPC2 loss of function in mammalian neurons.
Genetic deficiency of NPC1 or NPC2 results in a devastating cholesterol-glycosphingolipidosis of brain and other organs known as Niemann-Pick type C (NPC) disease. While NPC1 is a transmembrane protein believed involved in retroendocytic shuttling of substrate(s) to the Golgi and possibly elsewhere in cells as part of an essential recycling/homeostatic control mechanism, NPC2 is a soluble lysos...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2004
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.0308456101