Reactome | LDL:LDLR complex [plasma membrane] => LDL:LDLR complex [clathrin-coated vesicle] (LDLRAP1-independent)

LDL:LDLR complex [plasma membrane] => LDL:LDLR complex [clathrin-coated vesicle] (LDLRAP1-independent)

Stable Identifier

R-HSA-171141

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

Internalization of LDL:LDLR complex (LDLRAP1-independent)

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

LDL:LDLR complex [plasma membrane] => LDL:LDLR complex [clathrin-coated vesicle] (LDLRAP1-independent)

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Low density lipoprotein (LDL) particles bound to their receptors (LDLR) in coated pits on the cell surface are taken up into clathrin-coated vesicles (Goldstein et al. 1979). In hepatocytes and lymphocytes, but not in fibroblasts, this process requires the presence of an additional protein, LDLRAP1 (ARH1). In human patients, LDLRAP1 deficiency is associated with hypercholesterolemia, emphasizing the central role of the liver in clearance of circulating LDL in vivo (Eden et al. 2002; Garuti et al. 2005; He et al. 2002; Michaely et al. 2004). In vitro, LDLRAP1 protein binds both to LDLR and to components of the clathrin coat, suggesting that it might play an essential bridging function during the movement of LDL:LDLR complexes into clathrin-coated vesicles. This role has not yet been demonstrated in vivo, however, nor is it clear what might substitute for such a bridging function in fibroblasts.

Literature References

PubMed ID	Title	Journal	Year
15166224	The modular adaptor protein ARH is required for low density lipoprotein (LDL) binding and internalization but not for LDL receptor clustering in coated pits Hobbs, HH, Cohen, JC, Li, WP, Michaely, P, Anderson, RG	J Biol Chem	2004
12464675	Restoration of LDL receptor function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1 Eden, ER, Patel, DD, Neuwirth, C, Themis, M, Burden, JJ, Naoumova, RP, Lee, P, Edwards, M, Soutar, AK, Sun, XM	J Clin Invest	2002
12221107	ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2 Hobbs, HH, He, G, Gupta, S, Cohen, JC, Michaely, P, Yi, M	J Biol Chem	2002
221835	Coated pits, coated vesicles, and receptor-mediated endocytosis Goldstein, JL, Brown, MS, Anderson, RG	Nature	1979
16179341	The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits Garuti, R, Gerard, RD, Hobbs, HH, Herz, J, Jones, C, Cohen, JC, Li, WP, Michaely, P	J Biol Chem	2005