Scavenger receptors are a large and diverse superfamily of

cell surface receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

s. Its properties were first recorded in 1970 by Drs. Brown and Goldstein, with the defining property being the ability to bind and remove modified low density lipoproteins (LDL). Today scavenger receptors are known to be involved in a wide range of processes, such as: homeostasis, apoptosis, inflammatory diseases and pathogen clearance. Scavenger receptors are mainly found on

myeloid cells A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophilic ...

and other cells that bind to numerous ligands, primarily endogenous and modified host-molecules together with pathogen-associated molecular patterns(PAMPs), and remove them. The

Kupffer cells Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Ku ...

in the liver are particularly rich in scavenger receptors, includes SR-A I, SR-A II, and MARCO.

Function

The scavenger receptor superfamily is defined by its ability to recognize and bind a broad range of common ligands. These ligands include: polyanionic ligands including lipoproteins, apoptotic cells, cholesterol ester, phospholipids, proteoglycans, ferritin, and carbohydrates. This broad recognition range allows scavenger receptors to play an important role in homeostasis and the combating of diseases. This is accomplished via the recognition of various PAMP's and DAMP's, which leads to the removal or scavenging of pathogens with the recognition of PAMP's and the removal of apoptotic cells, self reactive antigens and the products of oxidative stress with the recognition of DAMP's. In

atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...

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 cell Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a plaque that can lead to atherosclerosis and trigger heart attacks and stroke. Foam cells are fat-laden cells with a M2 macrophage-like ...

s. Likewise, they secrete various inflammatory

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

s and accelerate the development of atherosclerosis.

Types

Scavenger receptors are incredibly diverse and therefore, organized into many different classes, starting at A and continuing to L. This organization is based on their structural properties. Due to the diversity and ongoing research into scavenger receptors, the receptors lack an accepted

nomenclature Nomenclature (, ) is a system of names or terms, or the rules for forming these terms in a particular field of arts or sciences. The principles of naming vary from the relatively informal conventions of everyday speech to the internationally ag ...

and have been described under different names. In 2014 a new nomenclature was proposed that has been used by some researchers, although no official recognition has been given. * Class A is mainly expressed in the macrophage, as a protein whose molecular weight is about 80

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...

and makes a trimer; it is composed of 1)

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

domain, 2)

transmembrane A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequent ...

domain, 3) spacer domain, 4)

alpha-helical The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ...

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

Class A receptors are a type II membrane protein who use their collagen-like domain for

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

binding. Members include:Scavenger receptors type 1 (SR-A1), which is a trimer with a molecular weight of about 220-250 kDa (the molecular weight of monomeric protein is about 80 kDa). It preferentially binds modified

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

, either acylated (acLDL) or oxidized (oxLDL). Other ligands include: β-amyloid, heat shock proteins, surface molecules of Gram-positive and Gram-negative bacteria, hepatitis C virus. SR-A1 can be alternatively spliced to generate a truncation at the C-terminus; it is contained within the Endoplasmatic Reticulum, and just like the unspliced version, has a strong affinity for polyanionic ligand binding. * SCARA1 or MSR1 (SR-A1): besides macrophages they can be found on smooth vascular muscle cells and endothelial tissues; oxidative stress enhances their presence on the endothelium. * SCARA2 or MARCO (SR-A6): only found on macrophages in the peritoneum, lymph nodes, liver and specific zones of the spleen. Bacteria and lipopolysaccharide produced by bacteria stimulate its expression; SR-A6 is unable to connect with modified LDL. * SCARA3, MSRL1 or APC7 (SR-A3): plays a significant role in the protection against reactive oxygen species ( ROS). * SCARA4 or

COLEC12 Collectin-12, also known as collectin subfamily member 12, is a collectin protein that in humans is encoded by the ''COLEC12'' gene. Function This gene encodes a member of the collectin family, proteins that possess collagen-like sequences and ...

(SR-A4): acts as a receptor for the detection, engulfment and destruction of oxidatively modified LDL for vascular endothelial cells. * SCARA5 or TESR (SR-A5): located in a diverse set of tissues, such as, lung placenta, intestine, heart and epithelial cells, it has a high affinity for bacteria but not for modified LDL.

Class B

CD36 CD36 (cluster of differentiation 36), also known as platelet glycoprotein 4, fatty acid translocase (FAT), scavenger receptor class B member 3 (SCARB3), and glycoproteins 88 (GP88), IIIb (GPIIIB), or IV (GPIV) is a protein that in humans is enco ...

and scavenger receptor class BI are identified as genes encoding for oxidized LDL receptors and classified into scavenger receptor B (SR-B). Both proteins have two transmembrane domains with an extracellular loop, and they are concentrated in a specific plasma membrane microdomain, the

caveolae In biology, caveolae ( Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50–100 nanometer) invaginations of the plasma membrane in the cells of many vertebrates. They are the most abundant surface ...

. Members include: *

SCARB1 Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the ''SCARB1'' gene. SR-BI functions as a receptor for high-density lipoprotein. Function Scavenger receptor class B, type I (SR-BI) is an i ...

or CD36L1 (SR-B1): can interact not only with oxidized LDL but also with normal

and high-density lipoproteins ( HDL), and plays an important role in their transportation into the cells. Recent studies have indicated that SR-B1 is likely to be the major receptor involved in HDL metabolism in mice and humans. Besides LDL and HDL, SR-B1 binds to viruses and bacteria. SR-B1 is located on hepatocytes, steroidogenic cells, arterial wall and macrophages. Mutations in SR-B1 have a negative effect on fertility and innate immune response, and leads to an increase in atherosclerosis. *

SCARB2 Lysosomal integral membrane protein 2 (LIMP-2) is a protein that in humans is encoded by the ''SCARB2'' gene. LIMP-2 is expressed in brain, heart, liver, lung and kidney, mainly in the membrane of lysosome organelles; however, in cardiac muscle, LI ...

* SCARB3 or

(SR-B2): has been thought to be implicated in cell adhesion, development of blood vessels, in the

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

of apoptotic cells, and in the

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

of long-chain

fatty acids In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an B ...

. Furthermore, it has been shown that CD36 is heavily involved with macrophage migration and signalling, together with protecting the host against, bacteria, fungi and malaria parasites. 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. CD36 can be found in many different cells, for example, insulin-responsive cells, hematopoietic cells like platelets, monocytes, and macrophages, endothelial cells, and specialized epithelial cells in the breast and the eye.

Other

Some receptors that can bind to oxidized LDL have been discovered. *

CD68 CD68 ( Cluster of Differentiation 68) is a protein highly expressed by cells in the monocyte lineage (e.g., monocytic phagocytes, osteoclasts), by circulating macrophages, and by tissue macrophages (e.g., Kupffer cells, microglia). Structure a ...

and its mouse homologue, macrosialin, has a unique N-terminal

mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...

-like domain. *

Mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...

is a naturally occurring viscous substance (such as found in many ''

nattō , spelled as natto in standard English language use, is a traditional Japanese food made from whole soybeans that have been fermented with ''Bacillus subtilis'' var. ''natto''. It is often served as a breakfast food with rice. It is served wi ...

'' or

okra Okra or Okro (, ), ''Abelmoschus esculentus'', known in many English-speaking countries as ladies' fingers or ochro, is a flowering plant in the mallow family. It has edible green seed pods. The geographical origin of okra is disputed, with su ...

) that is composed of a protein and covalently linked polysaccharides. A ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' class C scavenger receptor (dSR-C1) also has a

-like structure. * Lectin-like oxidized LDL receptor-1 ( LOX-1) was isolated from an aortic endothelial cell; recently, it has been discovered in macrophages and vascular

smooth muscle cell Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

s in artery vessels. The expression of LOX-1 is induced by inflammatory stimuli, so LOX-1 is thought to be involved in the development of

lesions.

References

External links

*
Human scavenger-like receptors
in Membranome database {{Pattern recognition receptors Receptors Single-pass transmembrane proteins