Signaling by the high-affinity HDL receptor scavenger receptor B type i

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Scavenger receptor B type I (SR-BI) plays an important role in mediating cholesterol exchange between cells, high-density lipoprotein (HDL) cholesterol, and other lipoproteins. SR-BI in hepatocytes is essential for reverse cholesterol transport and biliary secretion of HDL cholesterol; thus, it is atheroprotective. More recently, it has been discovered that the HDL-SR-BI tandem serves other functions that also likely contribute to HDL-related cardiovascular protection. A number of the latter mechanisms, particularly in endothelial cells, involve unique direct signal initiation by SR-BI that leads to the activation of diverse kinase cascades. SR-BI signaling occurs in response to plasma membrane cholesterol flux. It requires the C-terminal PDZ-interacting domain of the receptor, which mediates direct interaction with the adaptor molecule PDZK1; and the C-terminal transmembrane domain, which directly binds membrane cholesterol. In endothelium, direct SR-BI signaling in response to HDL results in enhanced production of the antiatherogenic molecule nitric oxide; in a nitric oxide-independent manner, it serves to maintain endothelial monolayer integrity. The role of SR-BI signaling in the numerous other cellular targets of HDL, including hepatocytes, macrophages, and platelets, and the basis by which SR-BI senses plasma membrane cholesterol movement to modify cell behavior are unknown. Further understanding of signaling by SR-BI will optimize the capacity to harness the mechanisms of action of HDL-SR-BI for cardiovascular benefit.

Original languageEnglish (US)
Pages (from-to)144-150
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume30
Issue number2
DOIs
StatePublished - Feb 2010

Fingerprint

Scavenger Receptors
Cholesterol
HDL Lipoproteins
HDL Cholesterol
Hepatocytes
Nitric Oxide
Cell Membrane
high density lipoprotein receptors
PDZ Domains
Lipoproteins
Endothelium
Phosphotransferases
Blood Platelets
Endothelial Cells
Cell Count
Macrophages

Keywords

  • Cholesterol
  • Endothelium
  • HDL
  • Signaling
  • SR-BI
  • Src kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Signaling by the high-affinity HDL receptor scavenger receptor B type i. / Saddar, Sonika; Mineo, Chieko; Shaul, Philip W.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 30, No. 2, 02.2010, p. 144-150.

Research output: Contribution to journalArticle

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