L-selectin

Mammalian protein found in Homo sapiens

L selectin, also known as CD62L, is a cell adhesion molecule found on the cell surface of leukocytes, and the blastocyst. It is coded for in the human by the SELL gene. L selectin belongs to the selectin family of proteins, which recognize sialylated carbohydrate groups containing a Sialyl LewisX (sLeX) determinant. L selectin plays an important role in both the innate and adaptive immune responses by facilitating leukocyte endothelial cell adhesion events. 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. 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.

The nature of the interactions between L selectin and ligand depends on many circumstances, primarily the location of anatomically defined sites in the high vessel venules (perivascular, extravascular and intravascular). Because of the diversity of L selectin ligands, signals that propagate downstream of L selectin provide information about the position of the leukocyte within the multistep adhesion cascade (binding, rolling, adhesion, and transmigration). While L selectin ligands on the apical side of the endothelium have long been characterized as receptors for binding and rolling, glycans enriched on the basolateral side and in the basement membrane likely control quite different signals. The binding lifetime of L selectin with apical ligands will be on the order of milliseconds, so in contrast, L selectin dependent adhesion in a microenvironment without hydrodynamic shear stress (e. g., within transmigrating pseudopods) will take seconds to minutes. 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.

L selectin is expressed constitutively on most circulating leukocytes. on the other hand the mouse sell gene is composed of 9 exons. 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.

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”). 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.

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. 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.

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