Selectin
Selectins (cluster of differentiation 62 or CD62) are a family of cell adhesion molecules (or CAMs). All selectins are single-chain transmembrane glycoproteins that share similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding[2]. Selectins bind to sugar moieties and so are considered to be a type of lectin, cell adhesion proteins that bind sugar polymers.[3]
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[edit] Types
There are three subsets of selectins:
- E-selectin (in endothelial cells)
- L-selectin (in leukocytes)
- P-selectin (in platelets and endothelial cells)
[edit] Etymology
The name selectin comes from the words "selected" and "lectins," which are a type of carbohydrate-recognizing proteins.
[edit] Function
During an inflammatory response, stimuli such as histamine and thrombin cause endothelial cells to mobilize P-selectin from stores inside the cell to the cell surface. In addition, cytokines such as TNF-alpha stimulate the expression of E-selectin and additional P-selectin a few hours later.
As the leukocyte rolls along the blood vessel wall, the distal lectin-like domain of the selectin binds to certain carbohydrate groups presented on proteins (such as PSGL-1) on the leukocyte, which slows the cell and allows it to leave the blood vessel and enter the site of infection. The low-affinity nature of selectins is what allows the characteristic "rolling" action attributed to leukocytes during the leukocyte adhesion cascade[2].
The best-characterized ligand for the three selectins is P-selectin glycoprotein ligand-1 (PSGL-1), which is a mucin-type glycoprotein expressed on all white blood cells.
Neutrophils and eosinophils bind to E-selectin. One of the reported ligands for E-selectin is the sialylated Lewis X Ag (sLe(x)). Eosinophils, like neutrophils, use sialylated, protease-resistant structures to bind to E-selectin, although the eosinophil expresses much lower levels of these structures on its surface. [4] Ligands for P-selectin on eosinophils and neutrophils are similar sialylated, protease-sensitive, endo-beta-galactosidase-resistant structures, clearly different than those reported for E-selectin, and suggest disparate roles for P-selectin and E-selectin during recruitment during inflammatory responses. [5]
[edit] Research
Selectins are involved in projects to treat osteoporosis, a disease that occurs when bone-creating cells called osteoblasts become too scarce. Osteoblasts develop from stem cells, and scientists hope to eventually be able to treat osteoporosis by adding stem cells to a patient’s bone marrow. Researchers have developed a way to use selectins to direct stem cells introduced into the vascular system to the bone marrow[6]. E-selectins are constitutively expressed in the bone marrow, and researchers have shown that tagging stem cells with a certain glycoprotein causes these cells to migrate to the bone marrow. Thus, selectins may someday be essential to a regenerative therapy for osteoporosis[7].
[edit] See also
[edit] References
- ^ PDB 1G1R; Somers WS, Tang J, Shaw GD, Camphausen RT (October 2000). "Insights into the molecular basis of leukocyte tethering and rolling revealed by structures of P- and E-selectin bound to SLe(X) and PSGL-1". Cell 103 (3): 467–79. doi:10.1016/S0092-8674(00)00138-0. PMID 11081633.
- ^ a b Cotran; Kumar, Collins (1998). Robbins Pathologic Basis of Disease. Philadelphia: W.B Saunders Company. ISBN 0-7216-7335-X.
- ^ Parham,Peter.The Immune System. 2nd ed. Garland Science: New York, 2005. pg. 244-245
- ^ Bochner BS, Sterbinsky SA, Bickel CA, Werfel S, Wein M, Newman W., BS; Sterbinsky, SA; Bickel, CA; Werfel, S; Wein, M; Newman, W (January 15, 1994). "Differences between human eosinophils and neutrophils in the function and expression of sialic acid-containing counterligands for E-selectin". J Immunol. 152 (2): 774–82. PMID 7506734.
- ^ Wein, M; Sterbinsky, SA; Bickel, CA; Schleimer, RP; Bochner, BS (1995). "Comparison of human eosinophil and neutrophil ligands for P-selectin: ligands for P-selectin differ from those for E-selectin". Am J Respir Cell Mol Biol. 12 (3): 315–9. PMID 7532979.
- ^ In the lab of Robert Sackstein Harvard University
- ^ Sackstein Lab
[edit] External links
- Sackstein Lab of Research
- Computer-generated movie of the mobilization of P-selectin inside a leukocyte at mcb.harvard.edu
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