L-selectin: Difference between revisions
Immcarle179 (talk | contribs) →Function: added subsection on Neutrophils and Monocytes. References included. |
Immcarle179 (talk | contribs) →Function: Added new section on Clinical Signifigance. Includes information on relevance of L-selectin to HIV, Abnormal Pregnancy, and Cancer. copied from User:Immcarle179/L-Selectin |
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=== Embryo === |
=== Embryo === |
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L-selectin is also present on the surface of human embryo trophoblasts prior to implantation into the uterus. Similar to its function in lymphocytes, L-selectin acts as a receptor to facilitate adhesion of the embryo to the site of invasion on the surface epithelium of the uterine endometrium. The embryo secretes human chorionic gonadotropin (hCG), which downregulates anti-adhesion factor, [[MUC-1]], located on the uterine epithelium at the site of invasion. Removal of MUC-1 exposes the oligosaccharide ligands of the uterine epithelium, thus allowing binding by the L-selectin receptor of the trophopblast cell, followed by embryo adhesion and invasion.<ref name="pmid22374510">{{cite journal | vauthors = James JL, Carter AM, Chamley LW | title = Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation? | journal = Placenta | volume = 33 | issue = 5 | pages = 327–334 | date = May 2012 | pmid = 22374510 | doi = 10.1016/j.placenta.2012.01.020 }}</ref> |
L-selectin is also present on the surface of human embryo trophoblasts prior to implantation into the uterus. Similar to its function in lymphocytes, L-selectin acts as a receptor to facilitate adhesion of the embryo to the site of invasion on the surface epithelium of the uterine endometrium. The embryo secretes human chorionic gonadotropin (hCG), which downregulates anti-adhesion factor, [[MUC-1]], located on the uterine epithelium at the site of invasion. Removal of MUC-1 exposes the oligosaccharide ligands of the uterine epithelium, thus allowing binding by the L-selectin receptor of the trophopblast cell, followed by embryo adhesion and invasion.<ref name="pmid22374510">{{cite journal | vauthors = James JL, Carter AM, Chamley LW | title = Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation? | journal = Placenta | volume = 33 | issue = 5 | pages = 327–334 | date = May 2012 | pmid = 22374510 | doi = 10.1016/j.placenta.2012.01.020 }}</ref> |
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== Clinical Significance == |
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==== '''Human Immunodeficiency Virus (HIV)''' ==== |
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L-selectin expressed on [[Cd4 t cell|CD4 T]] lymphocytes has been implicated in mediating adhesion and entry of [[HIV]]. L-selectin binds [[Envelope glycoprotein GP120|gp120]], one of the many glycans present on the HIV envelope. This binding allows for rolling adhesion to T cells and thus facilitates the binding of HIV to its target receptors <ref>{{Cite journal |last=Segura |first=Jason |last2=He |first2=Biao |last3=Ireland |first3=Joanna |last4=Zou |first4=Zhongcheng |last5=Shen |first5=Thomas |last6=Roth |first6=Gwynne |last7=Sun |first7=Peter D. |date=2021-09-29 |title=The Role of L-Selectin in HIV Infection |url=https://www.frontiersin.org/articles/10.3389/fmicb.2021.725741/full |journal=Frontiers in Microbiology |volume=12 |pages=725741 |doi=10.3389/fmicb.2021.725741 |issn=1664-302X |pmc=PMC8511817 |pmid=34659153}}</ref>. Infection of the cell triggers shedding of L-selectin. The loss of L-selectin likely aids in the release of new [[virus]] from the cell. |
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==== Abnormal Pregnancy and infertility ==== |
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The binding of L-selectin to its ligands plays an important role in embryo implantation during human pregnancy. Deficiency epithelial expression of L-selectin ligands has been associated with infertility, while increased expression has been implicated in [[Ectopic pregnancy|ectopic pregnancies]] <ref name=":13">{{Cite journal |last=Feng |first=Ying |last2=Ma |first2=Xue |last3=Deng |first3=Liwen |last4=Bin Yao |last5=Xiong |first5=Ying |last6=Wu |first6=Yilun |last7=Wang |first7=Lin |last8=Ma |first8=Qianhong |last9=Ma |first9=Fang |date=2017-01-23 |title=Role of Selectins and their Ligands in Human Implantation Stage |url=https://academic.oup.com/glycob/article-lookup/doi/10.1093/glycob/cwx009 |journal=Glycobiology |language=en |pages=cwx009 |doi=10.1093/glycob/cwx009 |issn=0959-6658}}</ref> |
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==== Cancer ==== |
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The adhesive properties of L-selectin have been shown to contribute to cancer progression. L-selectin interactions participate in trafficking of [[chronic lymphocytic leukemia]] cells to the lymph nodes where they are able to proliferate and evolve. Additionally, L-selectin interactions may play a role in [[metastasis]]<ref>{{Cite journal |last=Natoni |first=Alessandro |last2=Macauley |first2=Matthew S. |last3=O’Dwyer |first3=Michael E. |date=2016 |title=Targeting Selectins and Their Ligands in Cancer |url=https://www.frontiersin.org/article/10.3389/fonc.2016.00093 |journal=Frontiers in Oncology |volume=6 |doi=10.3389/fonc.2016.00093 |issn=2234-943X |pmc=PMC4834419 |pmid=27148485}}</ref>. |
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== References == |
== References == |
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Revision as of 22:10, 8 March 2022
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | SELL, CD62L, LAM1, LECAM1, LEU8, LNHR, LSEL, LYAM1, PLNHR, TQ1, selectin L | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 153240; MGI: 98279; HomoloGene: 539; GeneCards: SELL; OMA:SELL - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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L-selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes and the preimplantation embryo. It belongs to the selectin family of proteins, which recognize sialylated carbohydrate groups containing a Sialyl LewisX (sLeX) determinant.[5] L-selectin plays an important role in both the innate and adaptive immune responses by facilitating leukocyte-endothelial cell adhesion events.[6] These tethering interactions are essential for the trafficking of monocytes and neutrophils into inflamed tissue as well as the homing of lymphocytes to secondary lymphoid organs. L-selectin is also expressed by lymphoid primed hematopoietic stem cells and may participate in the migration of these stem cells to the primary lymphoid organs.[6] In addition to its function in the immune response, L-selectin is expressed on embryonic cells and facilitates the attachment of the blastocyst to the endometrial endothelium during human embryo implantation.[7]
L-selectin is composed of multiple structural regions: an N-terminus C-type lectin domain, an adjacent epidermal growth factor-like domain, two to the consensus repeat units homologous to those found in C3/C4-binding proteins, an extracellular cleavage site, a short transmembrane domain, and a cytoplasmic tail. It is cleaved by ADAM17.[6][8]
Ligands
- GlyCAM-1, found in the high endothelial venules of the lymph nodes.
- CD34, found on endothelial cells.
- MadCAM-1, found on endothelial cells of gut-associated lymphoid tissue.
- PSGL-1, binds with low affinity.
Expression
L-selectin is expressed constitutively on most circulating leukocytes[9]. Over time, these molecules are released through the process of ectodomain shedding and are replaced by newly synthesized L-selectin proteins. Ectodomain shedding is largely accomplished through cleavage by ADAM17.
L-selection is expressed on naive T cells and is rapidly shed following T cell priming [9]. L-selectin expression is re-activated in cytotoxic T cells once they exit the lymph node. Mature central memory T cells express L-selectin while effector memory cells do not. L-selectin is also expressed by naive B cells, with the loss of L-selectin distinguishing activated B cells destined to differentiate to antibody-secreting cells
L-selectin is expressed on circulating neutrophils and is shed following neutrophil priming [9]. Expression of L-selectin in neutrophils decreases with neutrophil aging. Classical monocytes express high levels of L-selectin while in circulation. Shedding of L-selectin from monocytes occurs during trans-endothelial migration.
L-selectin expression is also observed on oocytes and early-stage embryos. Blastocysts express L-selectin following, but not prior to emergence from the zona pellucida. An increase in L-selectin expression is observed when both the blastocyst and cytotrophoblast attach to the endometrium. L-selectin expression decreases by the 17th week of pregnancy, and remains low or non-existent until term (2017)[10].
Function
Lymophocytes
L-selectin acts as a "homing receptor" for lymphocytes to enter secondary lymphoid tissues via high endothelial venules. Ligands present on endothelial cells will bind to lymphocytes expressing L-selectin, slowing lymphocyte trafficking through the blood, and facilitating entry into a secondary lymphoid organ at that point.[11] The receptor is commonly found on the cell surfaces of T cells. Naive T-lymphocytes, which have not yet encountered their specific antigen, need to enter secondary lymph nodes to encounter their antigen. Central memory T-lymphocytes, which have encountered antigen, express L-selectin to localize in secondary lymphoid organs. Here they reside ready to proliferate upon re-encountering antigen. Effector memory T-lymphocytes do not express L-selectin, as they circulate in the periphery and have immediate effector functions upon encountering antigen. High expression of L-selectin on human bone marrow progenitor cells is an early sign of cells becoming committed to lymphoid differentiation.[12]
Neutrophils and Monocytes
Similar to its role in homing lymphocytes to secondary lymphoid tissues, L-selectin expressed on the surface of monocytes and neutrophils is essential for facilitating the first stage of adhesion to venule epithelial cells (known as the “rolling stage”) [13][14]. Adhesion to activated epithelial cells is a critical step in the immune response as it allows these immune cells to emigrate from the bloodstream into inflamed tissue. Prolonged rolling and transmigration of neutrophils can trigger shedding of L-selectin from the neutrophil plasma membrane[14]. The membrane-bound fragment left behind following cleavage of L-selectin has also been suggested to play a critical role in the interstitial chemotaxis of neutrophils along a cytokine gradient[13]. L-selectin shedding also occurs in monocytes; however, in these cells shedding is triggered only during trans-endothelial and not by earlier stages of the adhesion process[13]. The specific shedding of L-selectin from the leading migratory fronts of transmigrating monocytes suggests that this process plays a role in facilitating the directional migration of these cells (2019)[13].
Embryo
L-selectin is also present on the surface of human embryo trophoblasts prior to implantation into the uterus. Similar to its function in lymphocytes, L-selectin acts as a receptor to facilitate adhesion of the embryo to the site of invasion on the surface epithelium of the uterine endometrium. The embryo secretes human chorionic gonadotropin (hCG), which downregulates anti-adhesion factor, MUC-1, located on the uterine epithelium at the site of invasion. Removal of MUC-1 exposes the oligosaccharide ligands of the uterine epithelium, thus allowing binding by the L-selectin receptor of the trophopblast cell, followed by embryo adhesion and invasion.[15]
Clinical Significance
Human Immunodeficiency Virus (HIV)
L-selectin expressed on CD4 T lymphocytes has been implicated in mediating adhesion and entry of HIV. L-selectin binds gp120, one of the many glycans present on the HIV envelope. This binding allows for rolling adhesion to T cells and thus facilitates the binding of HIV to its target receptors [16]. Infection of the cell triggers shedding of L-selectin. The loss of L-selectin likely aids in the release of new virus from the cell.
Abnormal Pregnancy and infertility
The binding of L-selectin to its ligands plays an important role in embryo implantation during human pregnancy. Deficiency epithelial expression of L-selectin ligands has been associated with infertility, while increased expression has been implicated in ectopic pregnancies [17]
Cancer
The adhesive properties of L-selectin have been shown to contribute to cancer progression. L-selectin interactions participate in trafficking of chronic lymphocytic leukemia cells to the lymph nodes where they are able to proliferate and evolve. Additionally, L-selectin interactions may play a role in metastasis[18].
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000188404 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026581 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Ivetic, Aleksandar (2018-03). "A head-to-tail view of L-selectin and its impact on neutrophil behaviour". Cell and Tissue Research. 371 (3): 437–453. doi:10.1007/s00441-017-2774-x. ISSN 0302-766X. PMC 5820395. PMID 29353325.
{{cite journal}}: Check date values in:|date=(help) - ^ a b c Ivetic, Aleksandar; Hoskins Green, Hannah Louise; Hart, Samuel James (2019-05-14). "L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling". Frontiers in Immunology. 10: 1068. doi:10.3389/fimmu.2019.01068. ISSN 1664-3224. PMC 6527602. PMID 31139190.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Feng, Ying; Ma, Xue; Deng, Liwen; Bin Yao; Xiong, Ying; Wu, Yilun; Wang, Lin; Ma, Qianhong; Ma, Fang (2017-01-23). "Role of Selectins and their Ligands in Human Implantation Stage". Glycobiology: cwx009. doi:10.1093/glycob/cwx009. ISSN 0959-6658.
- ^ Tvaroška, Igor; Selvaraj, Chandrabose; Koča, Jaroslav (2020-06-19). "Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review". Molecules. 25 (12): 2835. doi:10.3390/molecules25122835. ISSN 1420-3049. PMC 7355470. PMID 32575485.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c Ivetic, Aleksandar; Hoskins Green, Hannah Louise; Hart, Samuel James (2019-05-14). "L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling". Frontiers in Immunology. 10: 1068. doi:10.3389/fimmu.2019.01068. ISSN 1664-3224. PMC 6527602. PMID 31139190.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Feng, Ying; Ma, Xue; Deng, Liwen; Bin Yao; Xiong, Ying; Wu, Yilun; Wang, Lin; Ma, Qianhong; Ma, Fang (2017-01-23). "Role of Selectins and their Ligands in Human Implantation Stage". Glycobiology: cwx009. doi:10.1093/glycob/cwx009. ISSN 0959-6658.
- ^ Robbins SL, Cotran RS, Kumar V, Collins T (1998). Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. ISBN 0-7216-7335-X.
- ^ Kohn LA, Hao QL, Sasidharan R, Parekh C, Ge S, Zhu Y, et al. (October 2012). "Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin". Nature Immunology. 13 (10): 963–971. doi:10.1038/ni.2405. PMC 3448017. PMID 22941246.
- ^ a b c d Ivetic, Aleksandar; Hoskins Green, Hannah Louise; Hart, Samuel James (2019-05-14). "L-selectin: A Major Regulator of Leukocyte Adhesion, Migration and Signaling". Frontiers in Immunology. 10: 1068. doi:10.3389/fimmu.2019.01068. ISSN 1664-3224. PMC 6527602. PMID 31139190.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ a b Ivetic, Aleksandar (2018-03). "A head-to-tail view of L-selectin and its impact on neutrophil behaviour". Cell and Tissue Research. 371 (3): 437–453. doi:10.1007/s00441-017-2774-x. ISSN 0302-766X. PMC 5820395. PMID 29353325.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ James JL, Carter AM, Chamley LW (May 2012). "Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?". Placenta. 33 (5): 327–334. doi:10.1016/j.placenta.2012.01.020. PMID 22374510.
- ^ Segura, Jason; He, Biao; Ireland, Joanna; Zou, Zhongcheng; Shen, Thomas; Roth, Gwynne; Sun, Peter D. (2021-09-29). "The Role of L-Selectin in HIV Infection". Frontiers in Microbiology. 12: 725741. doi:10.3389/fmicb.2021.725741. ISSN 1664-302X. PMC 8511817. PMID 34659153.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Feng, Ying; Ma, Xue; Deng, Liwen; Bin Yao; Xiong, Ying; Wu, Yilun; Wang, Lin; Ma, Qianhong; Ma, Fang (2017-01-23). "Role of Selectins and their Ligands in Human Implantation Stage". Glycobiology: cwx009. doi:10.1093/glycob/cwx009. ISSN 0959-6658.
- ^ Natoni, Alessandro; Macauley, Matthew S.; O’Dwyer, Michael E. (2016). "Targeting Selectins and Their Ligands in Cancer". Frontiers in Oncology. 6. doi:10.3389/fonc.2016.00093. ISSN 2234-943X. PMC 4834419. PMID 27148485.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)
External links
- L-Selectin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Immunology at MCG 1/physresp
- Overview of all the structural information available in the PDB for UniProt: P14151 (L-selectin) at the PDBe-KB.
Further reading
- Ryan US, Worthington RE (February 1992). "Cell-cell contact mechanisms". Current Opinion in Immunology. 4 (1): 33–37. doi:10.1016/0952-7915(92)90120-4. PMID 1375831.
- Nicholson IC (2003). "CD62L (L-selectin)". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 144–146. PMID 12144128.
- Ivetic A, Ridley AJ (December 2004). "The telling tail of L-selectin". Biochemical Society Transactions. 32 (Pt 6): 1118–1121. doi:10.1042/BST0321118. PMID 15506984.
- Lasky LA, Singer MS, Dowbenko D, Imai Y, Henzel WJ, Grimley C, et al. (June 1992). "An endothelial ligand for L-selectin is a novel mucin-like molecule". Cell. 69 (6): 927–938. doi:10.1016/0092-8674(92)90612-G. PMID 1376638. S2CID 9517058.
- Ord DC, Ernst TJ, Zhou LJ, Rambaldi A, Spertini O, Griffin J, Tedder TF (May 1990). "Structure of the gene encoding the human leukocyte adhesion molecule-1 (TQ1, Leu-8) of lymphocytes and neutrophils". The Journal of Biological Chemistry. 265 (14): 7760–7767. doi:10.1016/S0021-9258(19)38994-X. PMID 1692315.
- Bevilacqua M, Butcher E, Furie B, Furie B, Gallatin M, Gimbrone M, et al. (October 1991). "Selectins: a family of adhesion receptors". Cell. 67 (2): 233. doi:10.1016/0092-8674(91)90174-W. hdl:2027.42/29086. PMID 1717161. S2CID 35258400.
- Tedder TF, Isaacs CM, Ernst TJ, Demetri GD, Adler DA, Disteche CM (July 1989). "Isolation and chromosomal localization of cDNAs encoding a novel human lymphocyte cell surface molecule, LAM-1. Homology with the mouse lymphocyte homing receptor and other human adhesion proteins". The Journal of Experimental Medicine. 170 (1): 123–133. doi:10.1084/jem.170.1.123. PMC 2189363. PMID 2473156.
- Camerini D, James SP, Stamenkovic I, Seed B (November 1989). "Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor". Nature. 342 (6245): 78–82. doi:10.1038/342078a0. PMID 2509939. S2CID 4342053.
- Bowen BR, Nguyen T, Lasky LA (July 1989). "Characterization of a human homologue of the murine peripheral lymph node homing receptor". The Journal of Cell Biology. 109 (1): 421–427. doi:10.1083/jcb.109.1.421. PMC 2115458. PMID 2663882.
- Siegelman MH, Weissman IL (July 1989). "Human homologue of mouse lymph node homing receptor: evolutionary conservation at tandem cell interaction domains". Proceedings of the National Academy of Sciences of the United States of America. 86 (14): 5562–5566. doi:10.1073/pnas.86.14.5562. PMC 336895. PMID 2664786.
- Bajorath J, Aruffo A (November 1995). "A template for generation and comparison of three-dimensional selectin models". Biochemical and Biophysical Research Communications. 216 (3): 1018–1023. doi:10.1006/bbrc.1995.2722. PMID 7488174.
- Dianzani U, Bragardo M, Buonfiglio D, Redoglia V, Funaro A, Portoles P, et al. (May 1995). "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". European Journal of Immunology. 25 (5): 1306–1311. doi:10.1002/eji.1830250526. PMID 7539755. S2CID 37717142.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Brenner B, Gulbins E, Schlottmann K, Koppenhoefer U, Busch GL, Walzog B, et al. (December 1996). "L-selectin activates the Ras pathway via the tyrosine kinase p56lck". Proceedings of the National Academy of Sciences of the United States of America. 93 (26): 15376–15381. doi:10.1073/pnas.93.26.15376. PMC 26412. PMID 8986819.
- Zöllner O, Lenter MC, Blanks JE, Borges E, Steegmaier M, Zerwes HG, Vestweber D (February 1997). "L-selectin from human, but not from mouse neutrophils binds directly to E-selectin". The Journal of Cell Biology. 136 (3): 707–716. doi:10.1083/jcb.136.3.707. PMC 2134294. PMID 9024699.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Prakobphol A, Thomsson KA, Hansson GC, Rosen SD, Singer MS, Phillips NJ, et al. (April 1998). "Human low-molecular-weight salivary mucin expresses the sialyl lewisx determinant and has L-selectin ligand activity". Biochemistry. 37 (14): 4916–4927. doi:10.1021/bi972612a. PMID 9538010.
- Sassetti C, Tangemann K, Singer MS, Kershaw DB, Rosen SD (June 1998). "Identification of podocalyxin-like protein as a high endothelial venule ligand for L-selectin: parallels to CD34". The Journal of Experimental Medicine. 187 (12): 1965–1975. doi:10.1084/jem.187.12.1965. PMC 2212365. PMID 9625756.
- Malhotra R, Ward M, Sim RB, Bird MI (July 1999). "Identification of human complement Factor H as a ligand for L-selectin". The Biochemical Journal. 341 (1): 61–69. doi:10.1042/0264-6021:3410061. PMC 1220330. PMID 10377245.
- Bradley LM, Duncan DD, Tonkonogy S, Swain SL (September 1991). "Characterization of antigen-specific CD4+ effector T cells in vivo: immunization results in a transient population of MEL-14-, CD45RB- helper cells that secretes interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma". The Journal of Experimental Medicine. 174 (3): 547–559. doi:10.1084/jem.174.3.547. PMC 2118927. PMID 1678774.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.