CHAPTER 14 DISEASES INVOLVING THE GOLGI CALCIUM PUMP J. VANOEVELEN, L. DODE, L. RAEYMAEKERS, F. WUYTACK AND L. MISSIAEN Laboratory of Physiology, KULeuven Campus Gasthuisberg O&N1, Herestraat 49 bus 802, B-3000 Leuven, Belgium Abstract: Secretory-pathway Ca 2+ -transport ATPases (SPCA) provide the Golgi apparatus with Ca 2+ and Mn 2+ needed for the normal functioning of this organelle. Loss of one functional copy of the human SPCA1 gene (ATP2C1) causes Hailey-Hailey disease, a rare skin disorder characterized by recurrent blisters and erosions in the flexural areas. Here, we will review the properties and functional role of the SPCAs. The relationship between Hailey-Hailey disease and its defective gene (ATP2C1) will be adressed as well Keywords: SPCA, ATP2C1, ATP2C2, Hailey-Hailey disease, Golgi apparatus 1. INTRODUCTION Intracellular Ca 2+ stores release Ca 2+ in the cytosol to control a whole range of physiological processes depending on the amplitude, frequency and subcellular localization of the rise in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) (Berridge, 1993). The Ca 2+ concentration in the lumen of the store ([Ca 2+ ] l ) may however not become too low during this release process, since a sufficiently high [Ca 2+ ] l is needed for the normal synthesis, chaperone-dependent processing, glycosylation, sorting and eventual breakdown of newly formed proteins (Chanat and Huttner, 1991; Oda, 1992; Carnell and Moore, 1994; Meldolesi and Pozzan, 1998). The endoplasmic reticulum is the major agonist-sensitive intracellular Ca 2+ store (Berridge, 2002). Experiments using aequorin targeted to the Golgi apparatus however revealed that also the Golgi complex loses Ca 2+ during agonist stimulation (Pinton et al., 1998). Ca 2+ uptake in the Golgi apparatus is mediated by two groups of Ca 2+ pumps: the sarco(endo)plasmic-reticulum Ca 2+ -transport ATPases (SERCA) and the secretory- pathway Ca 2+ -transport ATPases (SPCA) consisting of SPCA1 and SPCA2. SPCA1 is expressed in all cells (Vanoevelen et al., 2005), whereas SPCA2 is only present in 385 E. Carafoli and M. Brini (eds.), Calcium Signalling and Disease, 385–404. © 2007 Springer.