Nogo-B receptor stabilizes Niemann-Pick type C2 protein and regulates intracellular cholesterol trafficking. Cell Metab 2009 Sep;10(3):208-18
Date
09/03/2009Pubmed ID
19723497Pubmed Central ID
PMC2739452DOI
10.1016/j.cmet.2009.07.003Scopus ID
2-s2.0-69149089283 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
The Nogo-B receptor (NgBR) is a recently identified receptor for the N terminus of reticulon 4B/Nogo-B. Other than its role in binding Nogo-B, little is known about the biology of NgBR. To elucidate a basic cellular role for NgBR, we performed a yeast two-hybrid screen for interacting proteins, using the C-terminal domain as bait, and identified Niemann-Pick type C2 protein (NPC2) as an NgBR-interacting protein. NPC2 protein levels are increased in the presence of NgBR, and NgBR enhances NPC2 protein stability. NgBR localizes primarily to the endoplasmic reticulum (ER) and regulates the stability of nascent NPC2. RNAi-mediated disruption of NgBR or genetic deficiency in NgBR lead to a decrease in NPC2 levels, increased intracellular cholesterol accumulation, and a loss of sterol sensing, all hallmarks of an NPC2 mutation. These data identify NgBR as an NPC2-interacting protein and provide evidence of a role for NgBR in intracellular cholesterol trafficking.
Author List
Harrison KD, Miao RQ, Fernandez-Hernándo C, Suárez Y, Dávalos A, Sessa WCMESH terms used to index this publication - Major topics in bold
AnimalsCHO Cells
Carrier Proteins
Cell Line
Cholesterol
Cholesterol, LDL
Cricetinae
Cricetulus
Endoplasmic Reticulum
Gene Knockdown Techniques
Glycoproteins
Humans
RNA, Small Interfering
Receptors, Cell Surface
Two-Hybrid System Techniques
Vesicular Transport Proteins
