Scavenger receptors are a group of receptors that recognize modified
low-density lipoprotein by oxidation or acetylation. This naming is based on a
function of cleaning: Scavenger receptors widely recognize and take up
macromolecules that have a negative charge, like modified LDL.
Function It is thought that scavenger receptors
participate in the removal of many foreign substances and waste materials
in the living body by extensive ligand specificity and a variety of receptor
molecules. In atherosclerotic lesions, macrophages
that express scavenger receptors on their plasma membrane take up the
oxidized LDL deposited in the blood vessel wall aggressively, and develop
into foam cells. Likewise they secrete various inflammatory cytokines and
accelerate the development of atherosclerosis.
Types Scavenger receptors are categorized into
classes A, B, and C according to their structural characteristics.
Class A is mainly expressed in the macrophage, and a protein whose
molecular weight is about 80 kDa makes a trimer; it is composed of 1) cytosol
domain, 2) transmembrane domain, 3) spacer domain, 4) alpha-helical
coiled-coil domain, 5) collagen-like domain, and 6) cysteine-rich domain.
Class B has two transmembrane regions. Class C is a transmembrane protein whose
N-terminus is located extracellularly. = Class A =
Scavenger receptors type 1 and 2 are trimers with a molecular weight of about
220-250 kDa. They preferentially bind modified LDL, either acylated or
oxidized. They have a collagen-like domain, which is essential for ligand
binding. Members include:
SCARA1 or MSR1: SR-A1 scavenger receptors have a cysteine-rich domain,
which can be found in a series of cell surface receptors and soluble proteins,
but SR-A2 do not. SCARA2 or MARCO: Another scavenger
receptor class A, MARCO, has collagen-like and cysteine-rich domains.
SCARA3 SCARA4 or COLEC12
SCARA5 = Class B =
CD36 and scavenger receptor class BI are identified as oxidized LDL receptors and
classified into class B. Both proteins have two transmembrane domains, and they
are concentrated in a specific plasma membrane microdomain, the caveolae.
Members include: SCARB1. SR-BI can interact not only with
oxidized LDL but also with normal LDL and high-density lipoproteins. Recent
studies have indicated that SR-BI is likely to be the major receptor involved
in HDL metabolism in mice and humans. SCARB2
SCARB3 or CD36. CD36 has been thought to be implicated in cell adhesion, in the
phagocytosis of apoptotic cells, and in the metabolism of long-chain fatty
acids. In experimental mice models of atherosclerosis in which the gene for
CD36 has been deleted, the mice have a greatly reduced number of
atherosclerotic lesions. = Other =
Some receptors that can bind to oxidized LDL have been discovered.
CD68 and its mouse homologue, macrosialin, has a unique N-terminal
mucin-like domain. Mucin is a viscous substance that is
composed of a protein and polysaccharides binding it. A Drosophila
class C scavenger receptor also has a mucin-like structure.
Lectin-like oxidized LDL receptor-1 was isolated from an aortic endothelial
cell, and recently it has been discovered in macrophages and vascular
smooth muscle cells in artery vessels. The expression of LOX-1 is inducted by
inflammatory stimuli, so LOX-1 is thought to be involved in the
development of atherosclerotic lesions. References
External links Scavenger receptors at the US National
Library of Medicine Medical Subject Headings