Thematic Review Series: Lipid Transfer Proteins Scavenger receptor B type 1: expression, molecular regulation, and cholesterol transport function

Abstract

Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake. It is most abundantly expressed in liver, where it provides cholesterol for bile acid synthesis, and in steroidogenic tissues, where it delivers cholesterol needed for storage or steroidogenesis in rodents. SR-B1 transcription is regulated by trophic hormones in the adrenal gland, ovary, and testis; in the liver and elsewhere, SR-B1 is subject to posttranscriptional and posttranslational regulation. SR-B1 operates in several metabolic processes and contributes to pathogenesis of atherosclerosis, inflammation, hepatitis C virus infection, and other conditions. Here, we summarize characteristics of the selective uptake pathway and involvement of microvillar channels as facilitators of selective HDL-CE uptake. We also present the potential mechanisms of SR-B1-mediated selective cholesterol transport; the transcriptional, posttranscriptional, and posttranslational regulation of SR-B1; and the impact of gene variants on expression and function of human SR-B1. A better understanding of this unique pathway and SR-B1's role may yield improved therapies for a wide variety of conditions.

The dengue virus non-structural protein 1 (NS1) use the scavenger receptor B1 as cell receptor in human hepatic and mosquito cells

“…The expression of SRB1 in liver cells has been widely reported (Shen et al 2019). To evaluate the expression of SRB1 in C6/36 cells, non-permeabilized C6/36 monolayers were immunolabeled with an antibody specific for human SRB1 and analyzed by confocal microscopy, using Huh-7 and Vero cells as controls.…”

“…The entry of a protein into a cell is a multifactorial process since the plasmatic membrane is a plethora of different kind of molecules determined by the origin of the cell, which in turn modulate the nature of proteins to be internalized (Walrant et al, 2017). In hepatic cells, SRB1 is the main receptor of the HDL, playing an important role in the homeostasis of lipoproteins circulating in serum (Shen et al 2019). Derived from the fact that NS1 is internalized in liver cells and is a lipoprotein in nature, in this work we present data indicating the participation of the SRB1 in the internalization process of DENV and ZIKV NS1 in hepatic and insect cells.…”

“…The scavenger receptor B type 1 (SRB1) or his human homolog CLA-1, is a 509 amino acid transmembrane glycoprotein containing an extracellular domain as a unique loop of 408 amino acids with multiple sites of N-glycosylation and a cysteine-rich region, 2 transmembrane domains of 22 and 23 amino acids and 2 cytoplasmatic N and C terminal domains of 9 and 44 amino acids, respectively (Shen et al, 2018). SRB1 is the physiologically relevant cell surface HDL receptor responsible for selective HDL-cholesteryl esters (HDL-CE) uptake mainly in liver, where it is most abundantly expressed, providing cholesterol for bile acid synthesis and controlling de plasma HDL levels (Acton et al, 1996; Shen, 2019). In insects as Drosophila melanogaster and Aedes aegypti , among others, homolog genes for SRB1 have been identified; however, their functions in fatty acid transport has not been studied in these organisms (Nichols et al, 2008).…”

Mechanisms of Transport and Delivery of Vitamin A and Carotenoids to the Retinal Pigment Epithelium

“…The particles also have amphipathic apoproteins on their surfaces which are recognized by cell surface lipoprotein receptors. The major receptors for LDL are the LDL receptors (LDLRs) that recognizes apoB, while HDL is recognized by a family of scavenger receptors, prominently scavenger receptor class B number 1 (SRB1) . The relevance of these receptors to the uptake of carotenoids by the RPE is discussed below.…”

Lipid Transfer Proteins: Introduction to the Thematic Review Series

“…This often occurs without the accompanying holo-lipoproprotein in a process known as selective cholesteryl ester uptake. Knowledge about this receptor is reviewed by Azhar and colleagues (10). It was the first "HDL" receptor identified, as its uptake of cholesteryl ester is mainly from HDL.…”