Reactome | NPC2 binds CHOL

NPC2 binds CHOL

Stable Identifier

R-HSA-8876472

Type

Reaction [binding]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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In macrophages, the hydrolysis of cholesteryl esters (CHESTs) is the rate-limiting step in the removal of free cholesterol (CHOL) from these cells. CHOL is transported via transport vesicles and can be used for cellular functions or removed from the cell by ABCA1 to create new HDL particles. Accumulation of CHESTs in macrophage foam cells is key to atherosclerotic plaque formation (Dubland & Francis 2015). Exit from lysosomes of CHOL derived from the hydrolysis of CHESTs in low-density lipoproteins (LDLs) requires the concerted effort of two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. In the first step, NPC2 binds unesterified CHOL that has been released from LDLs in the lumen of lysosomes (Liou et al. 2006).

Literature References

PubMed ID	Title	Journal	Year
25699256	Lysosomal acid lipase: at the crossroads of normal and atherogenic cholesterol metabolism Francis, GA, Dubland, JA	Front Cell Dev Biol	2015
17018531	NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols Dixit, SS, Stock, AM, Liou, HL, Tint, GS, Lobel, P, Xu, S	J. Biol. Chem.	2006