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Related Experiment Video

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Mapping the dynamic high-density lipoprotein synapse.

Kathrin Frey1, Lucia Rohrer2, Fabian Frommelt3

  • 1Institute of Translational Medicine, Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland; Institute for Clinical Chemistry University Hospital Zurich, Zurich, Switzerland.

Atherosclerosis
|August 24, 2023
PubMed
Summary

High-density lipoprotein (HDL) interactions with cells involve complex protein clusters called HDL synapses. These synapses, independent of scavenger receptor B1 (SR-B1), influence HDL uptake and offer new therapeutic targets.

Keywords:
Aminopeptidase nCD13ChemoproteomicsHDLHigh-density lipoproteinInteractomeLigand-receptor interactionsScavenger receptor B1SignalingSpacial proteotypingSurfaceome

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Area of Science:

  • Cell biology
  • Biochemistry
  • Molecular medicine

Background:

  • High-density lipoprotein (HDL) particles are heterogeneous and interact with cell surface proteins, influencing health and disease.
  • The mechanisms of HDL's long-range signaling and cell interactions are not fully understood.
  • HDL's complexity suggests multiple receptors form condition-dependent interaction clusters on cell surfaces.

Purpose of the Study:

  • To investigate HDL-receptor interactions using a discovery-driven approach.
  • To identify and characterize cell surface protein communities involved in HDL binding.
  • To understand the role of these communities in HDL function and cellular uptake.

Main Methods:

  • Utilized LUX-MS, a mass spectrometry-based and light-controlled proximity labeling strategy.
  • Performed surfaceome nanoscale organization analysis on hepatocytes and endothelial cells.
  • Investigated the functional impact of HDL synapse members by silencing individual proteins.

Main Results:

  • Identified a novel cell surface protein community termed the 'HDL synapse' associated with HDL binding.
  • Demonstrated that the endothelial HDL synapse, comprising 60 proteins, can assemble independently of scavenger receptor B1 (SR-B1).
  • Discovered that aminopeptidase N (AMPN/CD13) is an HDL synapse member that directly mediates HDL uptake in human aortic endothelial cells.

Conclusions:

  • Preformed cell surface protein complexes, or HDL synapses, modulate HDL function.
  • These findings suggest new theranostic (therapeutic and diagnostic) opportunities for HDL-related conditions.