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

Stable Identifier
Reaction [transition]
Homo sapiens
Internalization of LDL:LDLR complex (LDLRAP1-independent)
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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
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