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

Zhenze Zhao, Shanica Pompey, Hongyun Dong, Jian Weng, Rita Garuti, Peter Michaely

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1550-1559
Number of pages10
JournalJournal of Lipid Research
Volume54
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

LDL Receptors
Proteins
Nitric Oxide
Lipoproteins
oxidized low density lipoprotein
Autosomal Recessive Hypercholesterolemia
Clathrin
Post Translational Protein Processing
Nitric Oxide Synthase

Keywords

  • Autosomal recessive hypercholesterolemia protein
  • Low density lipoprotein receptor
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

S-nitrosylation of ARH is required for LDL uptake by the LDL receptor. / Zhao, Zhenze; Pompey, Shanica; Dong, Hongyun; Weng, Jian; Garuti, Rita; Michaely, Peter.

In: Journal of Lipid Research, Vol. 54, No. 6, 06.2013, p. 1550-1559.

Research output: Contribution to journalArticle

Zhao, Zhenze ; Pompey, Shanica ; Dong, Hongyun ; Weng, Jian ; Garuti, Rita ; Michaely, Peter. / S-nitrosylation of ARH is required for LDL uptake by the LDL receptor. In: Journal of Lipid Research. 2013 ; Vol. 54, No. 6. pp. 1550-1559.
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