Format

Send to

Choose Destination
See comment in PubMed Commons below
J Lipid Res. 2013 Jun;54(6):1550-9. doi: 10.1194/jlr.M033167. Epub 2013 Apr 7.

S-nitrosylation of ARH is required for LDL uptake by the LDL receptor.

Author information

1
Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.

Abstract

The LDL receptor (LDLR) relies upon endocytic adaptor proteins for internalization of lipoproteins. The results of this study show that the LDLR adaptor autosomal recessive hypercholesterolemia protein (ARH) requires nitric oxide to support LDL uptake. Nitric oxide nitrosylates ARH at C199 and C286, and these posttranslational modifications are necessary for association of ARH with the adaptor protein 2 (AP-2) component of clathrin-coated pits. In the absence of nitrosylation, ARH is unable to target LDL-LDLR complexes to coated pits, resulting in poor LDL uptake. The role of nitric oxide on LDLR function is specific for ARH because inhibition of nitric oxide synthase activity impairs ARH-supported LDL uptake but has no effect on other LDLR-dependent lipoprotein uptake processes, including VLDL remnant uptake and dab2-supported LDL uptake. These findings suggest that cells that depend upon ARH for LDL uptake can control which lipoproteins are internalized by their LDLRs through changes in nitric oxide.

KEYWORDS:

autosomal recessive hypercholesterolemia protein; low density lipoprotein receptor; nitric oxide

PMID:
23564733
PMCID:
PMC3646456
DOI:
10.1194/jlr.M033167
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center