Tetraspanin 18 (TSPAN18)

Unlike other tetraspanins, over-expression of Tspan18 in lymphocyte cell lines activated an NFAT/AP-1 reporter, which responds to calcium and MAPK signalling. In DT40 B cell lines, Tspan18 signalling was independent of Lyn, Syk, PLC2 and IP3 receptors, which are essential for B cell receptor signalling.

However, Tspan18 signalling did require extracellular calcium and the calcium-activated phosphatase calcineurin, which activates NFAT. Additional studies that included the Jurkat T cell line showed that Tspan18 could not activate the MAPK-responsive AP-1 promoter, but instead mimicked the effect of the calcium ionophore ionomycin. Over-expression of Tspan18 or other tetraspanins did not affect signalling by the platelet collagen receptor GPVI.