LDLR is bound by DAB2 and ARH

Stable Identifier
R-HSA-8863471
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
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

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
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
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
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
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created
Cite Us!