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
Article
in English
| 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 SREBPSCAP 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 SREBPSCAP 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Membrane Glycoproteins
/
Carrier Proteins
/
Niemann-Pick Diseases
/
Intracellular Signaling Peptides and Proteins
/
Endoplasmic Reticulum
/
Cholesterol, LDL
/
Membrane Proteins
Limits:
Animals
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2008
Type:
Article
/
Project document
Affiliation country:
China
Institution/Affiliation country:
Fujian Medical University/CN
/
Shandong University/CN
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