LDLR is bound by DAB2 and ARH

Stable Identifier
Reaction [binding]
Homo sapiens
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Internalization of the low density lipoprotein receptor (LDLR) depends on the recognition of its atypical FDNPVY sequence by the CLASP (clathrin-associated sorting protein) LDLRAP1 (also known as ARH) and DAB2, which may be functionally redundant (Chen et al, 1990; Morris et al, 2001; Mishra et al, 2002a; He et al, 2002; Mishra et al, 2002b; Zhou et al, 2003; Mishra et al, 2005). Both DAB2 and LDLRAP1 also interact with both clathrin and AP-2 as well as with PI(4,5)P2 in the plasma membrane (Morris et al, 2001; Mishar et al, 2002a; He et al, 2002; Mishra et al, 2002b; Zhou et al, 2003). Consistent with the notion that cargo contributes to the regulation of CCP formation, overexpression of LDLR results in an increase in abortive CCP turnover, a decrease in the rate of CCP maturation and an increase in CCP size in an LDLRAP1- and DAB2-dependent manner (Mettlen et al, 2010).

Literature References
PubMed ID Title Journal Year
15728179 Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein

Keyel, PA, Edeling, MA, Owen, DJ, Dupin, AL, Mishra, SK, Traub, LM

J. Biol. Chem. 2005
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
1968060 NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor

Goldstein, JL, Chen, WJ, Brown, MS

J. Biol. Chem. 1990
20231386 Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis

Yarar, D, Loerke, D, Mettlen, M, Danuser, G, Schmid, SL

J. Cell Biol. 2010
12451172 The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery

Watkins, SC, Mishra, SK, Traub, LM

Proc. Natl. Acad. Sci. U.S.A. 2002
12944396 Xenopus autosomal recessive hypercholesterolemia protein couples lipoprotein receptors with the AP-2 complex in oocytes and embryos and is required for vitellogenesis

Zhang, J, Zhou, Y, King, ML

J. Biol. Chem. 2003
11247302 Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2

Morris, SM, Cooper, JA

Traffic 2001
12234931 Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor

Watkins, SC, Hawryluk, MJ, Keyel, PA, Mishra, SK, Traub, LM, Agostinelli, NR

EMBO J. 2002
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