Developmental Cell
Volume 50, Issue 3, 5 August 2019, Pages 283-295.e5
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Article
Multimerization and Retention of the Scavenger Receptor SR-B1 in the Plasma Membrane

https://doi.org/10.1016/j.devcel.2019.05.026Get rights and content
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Highlights

  • SR-B1 behavior and internalization were assessed in live cells using an ScFv antibody

  • SR-B1 is retained at the plasma membrane of cells for several hours

  • Extensive SR-B1 multimerization allows the receptor to evade endocytosis

  • Disruption of multimerization impairs HDL binding and SR-B1 function at the membrane

Summary

Scavenger receptor B1 (SR-B1), the main receptor for high-density lipoprotein (HDL), is key in preventing atherosclerosis. It removes cholesterol from HDL, returning the lipid-poor lipoprotein to the circulation. To study the mechanisms controlling SR-B1 dynamics at the plasma membrane and its internalization rate, we developed a single-chain variable fragment (ScFv) antibody to image the receptor in live cells and track the behavior of single SR-B1 molecules. Unlike transferrin receptors, cholera-toxin-binding gangliosides, and bulk membrane markers, SR-B1 was internalized only marginally over hours. Plasmalemmal retention was not attributable to its C-terminal PDZ-binding domain or to attachment to the cortical cytoskeleton. Instead, SR-B1 undergoes multimerization into large metastable clusters that, despite being mobile in the membrane, fail to enter endocytic pathways. SR-B1 multimerization was impaired by mutating its C-terminal leucine zipper and by disrupting actin polymerization, causing rapid receptor internalization. Multimerization and plasmalemmal retention are critical for SR-B1 function.

Keywords

scavenger receptor
SR-B1
HDL
cholesterol
endocytosis
multimerization
retention
atherosclerosis
adrenal gland
liver

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The authors contributed equally

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