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

Research output: Contribution to journalReview articlepeer-review

81 Scopus citations


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
Issue number2
StatePublished - Feb 2010


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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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