Skin-deep Ca²⁺ signalling from the Golgi

The differentiation, adhesion and motility of keratinocytes - as in many cells - are controlled by intracellular Ca²⁺. Most non-excitable cells release Ca²⁺ from the endoplasmic reticulum (ER) to mediate Ca²⁺ signalling, but Alain Hovnanian, Theodora Mauro and colleagues now report that keratinocytes are unique in using Ca²⁺ stored in the Golgi (see p. 671). The skin disorder Darier disease is caused by mutations in ATP2A2, which encodes the Ca²⁺ ATPase SERCA2 that sequesters Ca²⁺ in the ER. The authors describe how keratinocytes from Darier disease patients respond normally to increases in extracellular Ca²⁺ levels (which provoke intracellular Ca²⁺ release) despite impaired ER Ca²⁺ stores. This normal response results from upregulation of the Golgi Ca²⁺ ATPase hSPCA1. Furthermore, inactivation of the gene encoding hSPCA1 - ATP2C1, mutations in which cause the skin disorder Hailey-Hailey disease - diminishes the viability of Darier disease keratinocytes. The authors therefore conclude that the Golgi Ca²⁺ ATPase plays an essential role in Ca²⁺ signalling in the keratinocyte.