Niemann-Pick type C1 protein influences the delivery of cholesterol to the SREBP: SCAP complex
Braz. j. med. biol. res
;
41(1): 26-33, Jan. 2008. ilus
Artigo
em Inglês
| LILACS
| ID: lil-469975
ABSTRACT
The proposed role of Niemann-Pick type C1 protein (NPC1) in the delivery of low-density lipoprotein (LDL) cholesterol to the sterol regulatory element binding protein (SREBP):SREBP cleavage activation protein (SCAP) complex in the endoplasmic reticulum has been largely based on indirect studies and remains contentious. The major aim of the present study was to assess whether NPC1 is involved in the delivery of LDL cholesterol to the SREBP:SCAP complex. A cell line stably expressing green fluorescence protein-SCAP was cultured in the presence of U18666A, which can induce a Niemann-Pick type C disease phenotype, in order to locate the SREBP:SCAP complex by fluorescence microscopy. Our major finding was that defective NPC1 caused a delay in the ability of LDL cholesterol to suppress SREBP processing. This was shown in a time-course experiment by the effect of LDL on green fluorescence protein-SCAP movement when cells were treated with pharmacological agents to induce a Niemann-Pick type C disease phenotype. We demonstrated directly by fluorescence microscopy that defective NPC1 causes a delay in LDL cholesterol delivery to the endoplasmic reticulum where SCAP senses cholesterol.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Glicoproteínas de Membrana
/
Proteínas de Transporte
/
Doenças de Niemann-Pick
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Retículo Endoplasmático
/
LDL-Colesterol
/
Proteínas de Membrana
Limite:
Animais
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2008
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
China
Instituição/País de afiliação:
Fujian Medical University/CN
/
Shandong University/CN
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