Faculty Collaboration Database

S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization. J Lipid Res 2017 Feb;58(2):325-338

Date

11/25/2016

Pubmed ID

27881715

Pubmed Central ID

PMC5282949

DOI

10.1194/jlr.M070706

Scopus ID

2-s2.0-85011295067 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

Author List

Lee MH, Appleton KM, El-Shewy HM, Sorci-Thomas MG, Thomas MJ, Lopes-Virella MF, Luttrell LM, Hammad SM, Klein RL

Authors

Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of Wisconsin
Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Biological Transport
Calcium
HEK293 Cells
Humans
Lipoproteins, HDL
Lysophospholipids
Organ Culture Techniques
Rats
Receptors, Lysosphingolipid
Scavenger Receptors, Class B
Signal Transduction
Sphingosine