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 ). 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.
