Kathrin Frey, Switzerland
ETH Zurich Institute of Molecular Systems Biology (IMSB)Presenter of 1 Presentation
The HDL synapse: Decoding a complex interaction network of HDL residing proteins and endothelial cell surface receptors
Abstract
Background and Aims
HDL is thought to affect human health through signalling events triggered by dynamic molecular interactions with cell surface receptors. Despite its system-wide relevance for human health, the molecular mode of action of HDL signalling is not known in detail. Due to the complexity of this particle we hypothesise that multiple receptors participate in HDL signalling, which together assemble to form a condition- and particle-dependent HDL synapse at the cell surface.
Methods
A newly in-house developed proximity labelling strategy termed LUX-MS enables the characterisation of complex ligand-receptor interactions. Receptors proximal to a cell surface bound ligand are tagged in a light-dependant manner and subsequently identified by mass spectrometry. Using LUX-MS we elucidated the HDL synapse, composed of the cell bound HDL proteome and its surrounding receptors, on an endothelial model system.
Results
We identified several HDL proteins, among these APOA1. Furthermore, we identified the known HDL receptor SCARB1 and other novel potential HDL interactors. A substantial number of these candidates were identified in a LUX-MS experiment directly targeting SCARB1 through an antibody, indicating that we captured the SCARB1 environment in the HDL synapse snapshot on endothelial cells.
Conclusions
We propose a new screening strategy to map the complex HDL interaction network at the cell surface. Our data supports the concept of an HDL synapse and receptor candidates are currently undergoing functional validation to prove their relevance in HDL signalling. These findings could provide the basis for the development of therapeutic modulators targeting new HDL receptors to improve prevention of coronary heart disease.