This gene encodes the class A macrophagescavenger receptors, which include three different types (1, 2, 3) generated by alternative splicing of this gene. These receptors or isoforms are trimeric integral membrane glycoproteins and have been implicated in many macrophage-associated physiological and pathological processes including atherosclerosis, Alzheimer's disease, and host defense. They were thought to be expressed macrophage-specific, but recently shown to be present on different dendritic cells classes, too.[3]
The isoforms type 1 and type 2 are functional receptors and are able to mediate the endocytosis of modified low density lipoproteins (LDLs). The isoform type 3 does not internalize modified LDL (acetyl-LDL) despite having the domain shown to mediate this function in the types 1 and 2 isoforms. It has an altered intracellular processing and is trapped within the endoplasmic reticulum, making it unable to perform endocytosis. The isoform type 3 can inhibit the function of isoforms type 1 and type 2 when co-expressed, indicating a dominant negative effect and suggesting a mechanism for regulation of scavenger receptor activity in macrophages.[1]
Biotechnology application
Macrophage scavenger receptor has been shown to mediate adhesion of macrophages and other cell lines to tissue culture plastic.[4]
↑Robbins AK, Horlick RA (August 1998). "Macrophage scavenger receptor confers an adherent phenotype to cells in culture". BioTechniques. 25 (2): 240–4. PMID9714883.
↑Nakamura, Toshinobu; Hinagata Jun-ichi; Tanaka Toshiki; Imanishi Takeshi; Wada Youichiro; Kodama Tatsuhiko; Doi Takefumi (Jan 2002). "HSP90, HSP70, and GAPDH directly interact with the cytoplasmic domain of macrophage scavenger receptors". Biochem. Biophys. Res. Commun. United States. 290 (2): 858–64. doi:10.1006/bbrc.2001.6271. ISSN0006-291X. PMID11785981.
Further reading
Asaoka H, Matsumoto A, Itakura H, Kodama T (1993). "[Structural and function of the human macrophage scavenger receptor]". Nippon Rinsho. 51 (6): 1677–83. PMID8391600.
Emi M, Asaoka H, Matsumoto A, et al. (1993). "Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene". J. Biol. Chem. 268 (3): 2120–5. PMID8093617.
Ashkenas J, Penman M, Vasile E, et al. (1993). "Structures and high and low affinity ligand binding properties of murine type I and type II macrophage scavenger receptors". J. Lipid Res. 34 (6): 983–1000. PMID8394868.
Resnick D, Chatterton JE, Schwartz K, et al. (1996). "Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain". J. Biol. Chem. 271 (43): 26924–30. doi:10.1074/jbc.271.43.26924. PMID8900177.
Hsu HY, Hajjar DP, Khan KM, Falcone DJ (1998). "Ligand binding to macrophage scavenger receptor-A induces urokinase-type plasminogen activator expression by a protein kinase-dependent signaling pathway". J. Biol. Chem. 273 (2): 1240–6. doi:10.1074/jbc.273.2.1240. PMID9422792.
Gough PJ, Greaves DR, Gordon S (1998). "A naturally occurring isoform of the human macrophage scavenger receptor (SR-A) gene generated by alternative splicing blocks modified LDL uptake". J. Lipid Res. 39 (3): 531–43. PMID9548586.
Teupser D, Thiery J, Seidel D (1999). "Alpha-tocopherol down-regulates scavenger receptor activity in macrophages". Atherosclerosis. 144 (1): 109–15. doi:10.1016/S0021-9150(99)00040-4. PMID10381284.
Nakamura T, Hinagata J, Tanaka T, et al. (2002). "HSP90, HSP70, and GAPDH directly interact with the cytoplasmic domain of macrophage scavenger receptors". Biochem. Biophys. Res. Commun. 290 (2): 858–64. doi:10.1006/bbrc.2001.6271. PMID11785981.
Tomokiyo R, Jinnouchi K, Honda M, et al. (2002). "Production, characterization, and interspecies reactivities of monoclonal antibodies against human class A macrophage scavenger receptors". Atherosclerosis. 161 (1): 123–32. doi:10.1016/S0021-9150(01)00624-4. PMID11882324.
Xu J, Zheng SL, Komiya A, et al. (2002). "Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk". Nat. Genet. 32 (2): 321–5. doi:10.1038/ng994. PMID12244320.
Kosswig N, Rice S, Daugherty A, Post SR (2003). "Class A scavenger receptor-mediated adhesion and internalization require distinct cytoplasmic domains". J. Biol. Chem. 278 (36): 34219–25. doi:10.1074/jbc.M303465200. PMID12819208.
Miller DC, Zheng SL, Dunn RL, et al. (2003). "Germ-line mutations of the macrophage scavenger receptor 1 gene: association with prostate cancer risk in African-American men". Cancer Res. 63 (13): 3486–9. PMID12839931.
Wang L, McDonnell SK, Cunningham JM, et al. (2003). "No association of germline alteration of MSR1 with prostate cancer risk". Nat. Genet. 35 (2): 128–9. doi:10.1038/ng1239. PMID12958598.
Nupponen NN, Wallén MJ, Ponciano D, et al. (2004). "Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSR1 in sporadic prostate cancer". Genes Chromosomes Cancer. 39 (2): 119–25. doi:10.1002/gcc.10308. PMID14695991.