Reactome | LDLR is bound by DAB2 and ARH

LDLR is bound by DAB2 and ARH

Stable Identifier

R-HSA-8863471

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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 Mishra, SK, Keyel, PA, Edeling, MA, Dupin, AL, Owen, DJ, Traub, LM	J. Biol. Chem.	2005
12221107	ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2 He, G, Gupta, S, Yi, M, Michaely, P, Hobbs, HH, Cohen, JC	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 Chen, WJ, Goldstein, JL, Brown, MS	J. Biol. Chem.	1990
20231386	Cargo- and adaptor-specific mechanisms regulate clathrin-mediated endocytosis Mettlen, M, Loerke, D, Yarar, D, Danuser, G, Schmid, SL	J. Cell Biol.	2010
12451172	The autosomal recessive hypercholesterolemia (ARH) protein interfaces directly with the clathrin-coat machinery Mishra, SK, Watkins, SC, 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 Zhou, Y, Zhang, J, 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 Mishra, SK, Keyel, PA, Hawryluk, MJ, Agostinelli, NR, Watkins, SC, Traub, LM	EMBO J.	2002