Ly6
LY6/urokinase-type plasminogen activator receptor (uPAR) is superfamily of proteins that share a common structure but their expression patterns and functions vary in different tissues. Ly6 are cysteine-rich proteins that form disulfide bridges and create LU domain. These proteins can be clasified as GPI-anchored on the cell membrane or secreted. They are expressed in various types of tissues and their expression dependent on the stage of cell differentiation.[1] This family was discovered in the 1970s[2], and these proteins are still used as markers of distinct stage of leukocyte differentiation.[3][4] These days, about 35 human and 61 mouse Ly6 family members are known.[1] Depending on expression in different tissues, Ly6 family members have different functions. For example, it is involved in cell proliferation, cell migration, intercellular interactions, maturation of immune cells, activation of macrophages, and cytokine production.[3][1] Their overexpression or deregulation of their function, for example due to point mutations, is associated with tumorogenesis and autoimmune diseases.[5][6][7]
Gene organization
Genes encoding Ly6 family proteins are located in the human genome are clustered and located on chromosomes 6,8, 11 and 19 in human genome. In the murine genome it is located on chromosomes 17, 15, 9 and 7, respectively.[5][3][1] The genes encoding a Ly6 family protein with one LU domain consist of 3 exons and 2 introns. The first exon encodes the signal peptide, exons 2 and 3 encode the LU domain, and exon 3 also encodes the GPI anchor.[1]
Protein structure
Ly6 proteins are characterized by the LU domain. Typically, they form one LU domain, but they can consist of multiple LU domains. The LU domain consists of 60-80 AA and contains 10 cysteines arranged in a specific spacing pattern that allows distinct disulfide bridges which allow the formation of the three-fingered (3F) structural motif.[5][1]
Based on their subcellular localization, these proteins are classified as GPI-anchored on the cell membrane or secreted.[1]
Expression
Although the Ly6 family members share a common structure, their expression varies in different tissues and is regulated depending on the stage of cell differentiation.
Many Ly6 family members are expressed in hematopoetic precursors and differentiated hematopoetic cells in a lineage-specific manner and making them useful cell surface markers for leukocytes, facilitating identification of distinct leukocyte sub-population.[3]
Further, the Ly6 family proteins are also expressed, for example, by sperm, neurons, keratinocytes and epithelial cells.[1]
Function
Ly6 family proteins have different functions depending on expression in different tissues. They play an important role in the immune response to infection and maintaining homeostasis in response to varying environmental conditions. It is involved in cell proliferation, cell migration, intercellular interactions, maturation of immune cells, activation of macrophages and production of cytokines. It is also involved in complement activity, neuronal activity, angiogenesis, tumorogenesis and wound healing.[3][1]
Clinical relevance
Ly6 family proteins except of SLURP1 are over-expressed in inflammatory environment and tumor tissue. They are therefore used as tumor markers and also therapeutic targets.[1][2][6][5]
Some point mutations in Ly6 family proteins are associated with autoimmune diseases, such as psoriasis vulgaris.[5]
Ly6 proteins
References
- ^ a b c d e f g h i j Loughner, Chelsea L.; Bruford, Elspeth A.; McAndrews, Monica S.; Delp, Emili E.; Swamynathan, Sudha; Swamynathan, Shivalingappa K. (2016-12). "Organization, evolution and functions of the human and mouse Ly6/uPAR family genes". Human Genomics. 10 (1). doi:10.1186/s40246-016-0074-2. ISSN 1479-7364. PMC 4839075. PMID 27098205.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b McKenzie, I. F.; Gardiner, J.; Cherry, M.; Snell, G. D. (1977-3). "Lymphocyte antigens: Ly-4, Ly-6, and Ly-7". Transplantation Proceedings. 9 (1): 667–669. ISSN 0041-1345. PMID 68598.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c d e Kong, HK; Park, JH (November 2012). "Characterization and function of human Ly-6/uPAR molecules". BMB Reports. 45 (11): 595–603. doi:10.5483/bmbrep.2012.45.11.210. PMC 4133805. PMID 23186997.
- ^ Lee, P. Y.; Wang, J.-X.; Parisini, E.; Dascher, C. C.; Nigrovic, P. A. (29 March 2013). "Ly6 family proteins in neutrophil biology". Journal of Leukocyte Biology. 94 (4): 585–594. doi:10.1189/jlb.0113014. PMID 23543767.
- ^ a b c d e Upadhyay, Geeta (2019). "Emerging Role of Lymphocyte Antigen-6 Family of Genes in Cancer and Immune Cells". Frontiers in Immunology. 10. doi:10.3389/fimmu.2019.00819. ISSN 1664-3224. PMC 6491625. PMID 31068932.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b Archivum Immunologiae et Therapiae Experimentalis. Springer Nature.
- ^ Sidenius, Nicolai; Blasi, Francesco (2003-6). "The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy". Cancer Metastasis Reviews. 22 (2–3): 205–222. ISSN 0167-7659. PMID 12784997.
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