title: The new obesity-associated protein, neuronal growth regulator 1 (NEGR1), is implicated in Niemann-Pick disease Type C (NPC2)-mediated cholesterol trafficking.
abstract: Neuronal growth regulator 1 (NEGR1) is a newly identified raft-associated protein, which has recently been spotlighted as a new locus related to human obesity. Niemann-Pick disease Type C2 (NPC2) protein functions as a key player in the intracellular cholesterol trafficking, and its defect is linked to a fatal human neurodegenerative disease, NPC. In this study, we identified that NEGR1 interacts with NPC2 and increases its protein stability. Ectopically expressed NEGR1 proteins relieved an abnormal cholesterol accumulation in endosomal compartments. Importantly, NEGR1-defective mouse embryonic fibroblast cells exhibit increased cholesterol levels and triglyceride contents. These findings provide the first insight into the role of NEGR1 in intracellular cholesterol homeostasis, possibly explaining the missing link between NEGR1 with human obesity.
authors.affiliation: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Chun
authors.affiliation: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Lihua
authors.initials: L
authors.lastname: Che
authors.affiliation: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Jeongbeom
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Dentistry, Seoul National University, Seoul, 03080, Republic of Korea.
authors.forename: Sungjoong
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon, 34134, Republic of Korea. Electronic address: leesoojin@cnu.ac.kr.
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000737:chemistry*; D011992:Endosomes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D021962:Membrane Microdomains; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000378:metabolism; D052556:Niemann-Pick Disease, Type C / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D016366:Open Reading Frames; D014280:Triglycerides / Q000737:chemistry
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C485559:NEGR1 protein, human; D014280:Triglycerides; D002784:Cholesterol
keywords: Cholesterol; Lipid raft; Neuronal growth regulator 1; Niemann-Pick disease; Obesity; Type C2