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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.