Role of tetraspanins in mast cells

Mast cell (MC) degranulation basically is the result of FceRI cross-linking by IgE bound antigen. However, this process is mediated by a complex signaling machinery, sometimes referred to as the FceRI signalosome (1). Tetraspanin proteins have been named after their four transmembrane domains that incorporate several conserved motifs (2). They are often described as scaffold proteins that enable clustering of other membrane proteins, such bringing together various partners of intracellular signaling cascades (3) or increasing the density of some receptors (e.g. integrins) at some location at the extracellular side of the membrane (4). But tetraspanins are not restricted to the plasma membrane, they also reside in the membranes of intracellular compartments. An example for this is CD63, that is residing in the membranes of granules of various cell types as well and has long been known as an activation marker of human mast cells and basophils (5). However, CD63 and other tetraspanins are not just markers, but also modulators of MC degranulation by mediating clustering of FceRI and co-clustering of additional membrane molecules important for successful FceRI signaling. Surprisingly, they fine tune also additional MC functions (6).