NKp30/CD337 Protein

Siglec-4, also known as myelin-associated glycoprotein (MAG) is a 100 kDa glycoprotein located at the innermost layer of myelin sheets that remains in intimate contact with the axonal membrane. It is selectively expressed by myelinating cells including Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). MAG, a member of the sialic binding, immunoglobulin-like lectin (siglec) family, is a critical component of axon-glia interactions with multiple functions in the biology of both neurons and glial cells. A membrane-bound protein, MAG contains five extracellular immunoglobulin-like domains, and the NH2-terminal V-type immunoglobulin domain also contains the lectin domain. Known ligands for MAG include both proteins and glycolipids. It functions both as a ligand for an axonal receptor that is needed for the maintenance of myelinated axons and as a receptor for an axonal signal that promotes the differentiation, maintenance and survival of oligodendrocytes. MAG is expressed as two developmentally regulated isoforms with different cytoplasmic domains that may activate different signal transduction pathways in myelin-forming cells.Natural killer protein 30 (NKp30; also known as natural cytotoxicity receptor 3, NCR3; or CD337) is an Ig-like activating receptor of NK cells regulating the cross talk between NK and dendritic cells. It is expressed on the surface of NK cells, recently-expanded γδT cells, activated CD8 cells, and innate lymphocytes. The extracellular part of NKp30 consists of a single N-terminal Ig-like domain, followed by a distinct 15 amino acids long stalk region proximal to the plasma membrane, which is important for receptor signaling. Further, three specific cellular ligands of NKp30 have been identified. NKp30 binds a member of B7 family, in particular B7 homolog 6 (B7-H6). Interaction of NCR3 with B7H6 leads to activation of NK cells and induces cytolysis of target cells resulting in apoptotic cell death. Another NKp30 cellular ligand, BAG-6 is recruited to the cell membrane and interacts with NKp30 in some tumor cells or under the stress conditions. The most recently discovered NKp30 ligand, galectin 3, expressed on the surface of some tumors, almost completely blocks NK cell cytotoxicity.