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
integral membrane protein found in numerous cell types/tissues, including
enterocyte
Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase its ...
s, the
liver and
adrenal
The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
gland. It is best known for its role in facilitating the uptake of cholesteryl esters from
high-density lipoproteins in the liver. This process drives the movement of
cholesterol from peripheral tissues towards the
liver, where cholesterol can either be secreted via the bile duct or be used to synthesise steroid hormones.
This movement of
cholesterol is known as
reverse cholesterol transport
Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream.
Cholesterol from non-hepatic peripheral ti ...
and is a protective mechanism against the development of
atherosclerosis, which is the principal cause of
heart disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
and
stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
.
SR-BI is crucial in
carotenoid
Carotenoids (), also called tetraterpenoids, are yellow, orange, and red organic compound, organic pigments that are produced by plants and algae, as well as several bacteria, and Fungus, fungi. Carotenoids give the characteristic color to pumpki ...
and
vitamin E uptake in the small intestine.
SR-B1 is upregulated in times of vitamin A deficiency and downregulated if vitamin A status is in the normal range.
In melanocytic cells SCARB1 gene expression may be regulated by the
MITF
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the ''MITF'' gene.
MITF is a basic helix-loop-helix leucine zipper transcription factor ...
.
Species distribution
SR-BI has also been identified in the livers of non-mammalian species (
turtle,
goldfish,
shark,
chicken,
frog, and
skate
Skate or Skates may refer to: Fish
*Skate (fish), several genera of fish belonging to the family Rajidae
* Pygmy skates, several genera of fish belonging to the family Gurgesiellidae
* Smooth skates or leg skates, several genera of fish belongin ...
), suggesting it emerged early in vertebrate evolutionary history. The turtle also seems to upregulate SR-BI during
egg development, indicating that cholesterol efflux may be at peak levels during developmental stages.
Clinical significance
SCARB1 along with
CD81 is the receptor for the entry of the
Hepatitis C virus into liver cells.
Preclinical research
Although malignant tumors are known to display extreme
heterogeneity, overexpression of SR-B1 is a relatively consistent marker in cancerous tissues. While SR-B1 normally mediates the transfer of cholesterol between
high-density lipoproteins (HDL) and healthy cells, it also facilitates the selective uptake of cholesterol by malignant cells. In this way, upregulation of the SR-B1 receptor becomes an enabling factor for self-sufficient
proliferation
Proliferation may refer to:
Weapons
*Nuclear proliferation, the spread of nuclear weapons, material, and technology
*Chemical weapon proliferation, the spread of chemical weapons, material, and technology
* Small arms proliferation, the spread of ...
in cancerous tissue.
SR-B1 mediated delivery has also been used in the transfection of cancer cells with
siRNA, or small interfering RNAs. This therapy causes RNA interference, in which short segments of double stranded RNA acts to silence targeted
oncogenes post-transcription. SR-B1 mediation reduces siRNA degradation and off-target accumulation while enhancing delivery to targeted tissues. In "metastatic and
taxane
Taxanes are a class of diterpenes. They were originally identified from plants of the genus ''Taxus'' (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA ap ...
-resistant models of ovarian cancer, rHDL-mediated siren delivery improved responses.
Interactive pathway map
References
Further reading
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Scavenger receptors