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Dev Cell. 2019 Jun 4. pii: S1534-5807(19)30424-1. doi: 10.1016/j.devcel.2019.05.026. [Epub ahead of print]

Multimerization and Retention of the Scavenger Receptor SR-B1 in the Plasma Membrane.

Author information

1
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
2
Ceinge Biotecnologie Avanzate S.C.R.L., Naples, Campania 80131, Italy.
3
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
4
Cell Biology Program, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5C 1N8, Canada. Electronic address: sergio.grinstein@sickkids.ca.

Abstract

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:

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

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