SCARB1 explained

Scavenger receptor class B type 1 (SRB1) also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene.^[1] SR-BI functions as a receptor for high-density lipoprotein.^[2]

Function

Scavenger receptor class B, type I (SR-BI) is an integral membrane protein found in numerous cell types/tissues, including enterocytes, the liver and adrenal 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.^[3] This movement of cholesterol is known as reverse cholesterol transport and is a protective mechanism against the development of atherosclerosis, which is the principal cause of heart disease and stroke.

SR-BI is crucial in carotenoid and vitamin E uptake in the small intestine.^{[4] [5]} SR-B1 is upregulated in times of vitamin A deficiency and downregulated if vitamin A status is in the normal range.^[6]

In melanocytic cells SCARB1 gene expression may be regulated by the MITF.^[7]

Species distribution

SR-BI has also been identified in the livers of non-mammalian species (turtle, goldfish, shark, chicken, frog, and skate), 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.^[8]

Clinical significance

SCARB1 along with CD81 is the receptor for the entry of the Hepatitis C virus into liver cells.^[9]

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 in cancerous tissue.^{[10] [11]}

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-resistant models of ovarian cancer, rHDL-mediated siren delivery improved responses.^[12]

Further reading

• Williams DL, Temel RE, Connelly MA . Roles of scavenger receptor BI and APO A-I in selective uptake of HDL cholesterol by adrenal cells . Endocrine Research . 26 . 4 . 639–51 . November 2000 . 11196441 . 10.3109/07435800009048584 . 21441940 .
• Krause BR, Auerbach BJ . Reverse cholesterol transport and future pharmacological approaches to the treatment of atherosclerosis . Current Opinion in Investigational Drugs . 2 . 3 . 375–81 . March 2001 . 11575708 .
• Connelly MA, Williams DL . Scavenger receptor BI: a scavenger receptor with a mission to transport high density lipoprotein lipids . Current Opinion in Lipidology . 15 . 3 . 287–95 . June 2004 . 15166784 . 10.1097/00041433-200406000-00008 . 24035736 .
• Phillips RW . The new era in restorative dental materials . Operative Dentistry . 1 . 1 . 29–35 . 1978 . 1076467 .
• Skre H, Berg K . Cerebellar ataxia and total albinism: a kindred suggesting pleitotropism or linkage . Clinical Genetics . 5 . 3 . 196–204 . 1974 . 4838888 . 10.1111/j.1399-0004.1974.tb01682.x . 37259762 .
• Calvo D, Dopazo J, Vega MA . The CD36, CLA-1 (CD36L1), and LIMPII (CD36L2) gene family: cellular distribution, chromosomal location, and genetic evolution . Genomics . 25 . 1 . 100–6 . January 1995 . 7539776 . 10.1016/0888-7543(95)80114-2 .
• Calvo D, Vega MA . Identification, primary structure, and distribution of CLA-1, a novel member of the CD36/LIMPII gene family . The Journal of Biological Chemistry . 268 . 25 . 18929–35 . September 1993 . 10.1016/S0021-9258(17)46716-0 . 7689561 . free .
• Murao K, Terpstra V, Green SR, Kondratenko N, Steinberg D, Quehenberger O . Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes . The Journal of Biological Chemistry . 272 . 28 . 17551–7 . July 1997 . 9211901 . 10.1074/jbc.272.28.17551 . free .
• Ikemoto M, Arai H, Feng D, Tanaka K, Aoki J, Dohmae N, Takio K, Adachi H, Tsujimoto M, Inoue K . Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I . Proceedings of the National Academy of Sciences of the United States of America . 97 . 12 . 6538–43 . June 2000 . 10829064 . 18651 . 10.1073/pnas.100114397 . 2000PNAS...97.6538I . free .
• Husemann J, Silverstein SC . Expression of scavenger receptor class B, type I, by astrocytes and vascular smooth muscle cells in normal adult mouse and human brain and in Alzheimer's disease brain . The American Journal of Pathology . 158 . 3 . 825–32 . March 2001 . 11238031 . 1850374 . 10.1016/S0002-9440(10)64030-8 .
• Li XA, Titlow WB, Jackson BA, Giltiay N, Nikolova-Karakashian M, Uittenbogaard A, Smart EJ . High density lipoprotein binding to scavenger receptor, Class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner . The Journal of Biological Chemistry . 277 . 13 . 11058–63 . March 2002 . 11792700 . 10.1074/jbc.M110985200 . free .
• Duncan KG, Bailey KR, Kane JP, Schwartz DM . Human retinal pigment epithelial cells express scavenger receptors BI and BII . Biochemical and Biophysical Research Communications . 292 . 4 . 1017–22 . April 2002 . 11944916 . 10.1006/bbrc.2002.6756 .
• Kawasaki Y, Nakagawa A, Nagaosa K, Shiratsuchi A, Nakanishi Y . Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells . The Journal of Biological Chemistry . 277 . 30 . 27559–66 . July 2002 . 12016218 . 10.1074/jbc.M202879200 . free .
• Qi C, Chang J, Zhu Y, Yeldandi AV, Rao SM, Zhu YJ . Identification of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha . The Journal of Biological Chemistry . 277 . 32 . 28624–30 . August 2002 . 12039952 . 10.1074/jbc.M201053200 . free .
• Johnson MS, Svensson PA, Borén J, Billig H, Carlsson LM, Carlsson B . Expression of scavenger receptor class B type I in gallbladder columnar epithelium . Journal of Gastroenterology and Hepatology . 17 . 6 . 713–20 . June 2002 . 12100619 . 10.1046/j.1440-1746.2002.02776.x . 21584794 .
• Silver DL . A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver . The Journal of Biological Chemistry . 277 . 37 . 34042–7 . September 2002 . 12119305 . 10.1074/jbc.M206584200 . free .
• Bultel-Brienne S, Lestavel S, Pilon A, Laffont I, Tailleux A, Fruchart JC, Siest G, Clavey V . Lipid free apolipoprotein E binds to the class B Type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from lipoproteins . The Journal of Biological Chemistry . 277 . 39 . 36092–9 . September 2002 . 12138091 . 10.1074/jbc.M201943200 . free .
• Strauss JG, Zimmermann R, Hrzenjak A, Zhou Y, Kratky D, Levak-Frank S, Kostner GM, Zechner R, Frank S . Endothelial cell-derived lipase mediates uptake and binding of high-density lipoprotein (HDL) particles and the selective uptake of HDL-associated cholesterol esters independent of its enzymic activity . The Biochemical Journal . 368 . Pt 1 . 69–79 . November 2002 . 12164779 . 1222966 . 10.1042/BJ20020306 .

Notes and References

1. Web site: Entrez Gene: SCARB1 Scavenger receptor class B, member 1.
2. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M . Identification of scavenger receptor SR-BI as a high density lipoprotein receptor . Science . 271 . 5248 . 518–20 . January 1996 . 8560269 . 10.1126/science.271.5248.518 . 1996Sci...271..518A . 249922 .
3. Rhainds D, Brissette L . The role of scavenger receptor class B type I (SR-BI) in lipid trafficking. defining the rules for lipid traders . The International Journal of Biochemistry & Cell Biology . 36 . 1 . 39–77 . January 2004 . 14592533 . 10.1016/s1357-2725(03)00173-0.
4. Valacchi G, Sticozzi C, Lim Y, Pecorelli A . Scavenger receptor class B type I: a multifunctional receptor . Annals of the New York Academy of Sciences . 1229 . 1. E1-7 . July 2011 . 22239457 . 10.1111/j.1749-6632.2011.06205.x . 2011NYASA1229E...1V . 7844031 . free .
5. van Bennekum A, Werder M, Thuahnai ST, Han CH, Duong P, Williams DL, Wettstein P, Schulthess G, Phillips MC, Hauser H . 6 . Class B scavenger receptor-mediated intestinal absorption of dietary beta-carotene and cholesterol . Biochemistry . 44 . 11 . 4517–25 . March 2005 . 15766282 . 10.1021/bi0484320 .
6. Book: Blaner WS . Present Knowledge in Nutrition, Eleventh Edition . Vitamin A . BP Marriott . DF Birt . VA Stallings. AA Yates . Academic Press (Elsevier) . 2020 . London, United Kingdom . 73–92 . 978-0-323-66162-1.
7. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell & Melanoma Research . 21 . 6 . 665–76 . December 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . free .
8. Duggan AE, Marie RS, Callard IP . Expression of SR-BI (Scavenger Receptor Class B Type I) in turtle (Chrysemys picta) tissues and other nonmammalian vertebrates . The Journal of Experimental Zoology . 292 . 5 . 430–4 . April 2002 . 11857477 . 10.1002/jez.10067 .
9. Kapadia SB, Barth H, Baumert T, McKeating JA, Chisari FV . Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I . Journal of Virology . 81 . 1 . 374–83 . January 2007 . 17050612 . 1797271 . 10.1128/JVI.01134-06 .
10. Mooberry LK, Sabnis NA, Panchoo M, Nagarajan B, Lacko AG . Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging . Frontiers in Pharmacology . 7 . 466 . 466 . December 2016 . 28018216 . 10.3389/fphar.2016.00466 . 5156841. free .
11. Gutierrez-Pajares JL, Ben Hassen C, Chevalier S, Frank PG . SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer . Frontiers in Pharmacology . 7 . 338 . 2016 . 27774064 . 5054001 . 10.3389/fphar.2016.00338 . free .
12. Rajora MA, Zheng G . Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy . Frontiers in Pharmacology . 7 . Art. 326 . 326 . 2016 . 27729859 . 10.3389/fphar.2016.00326 . 5037127. free .