Ca2+/Mn2+ pumps of the Golgi apparatus and Hailey–Hailey disease

Abstract

All compartments of the secretory pathway require a sufficiently high luminal Ca 2+ (and Mn 2+ ) concentration ([Ca 2+ ] l ) to carry out their respective functions. The Ca 2+ -uptake mechanism of the endoplasmic reticulum (ER) consists of the well-characterized sarco(endo)plasmic reticulum Ca 2+ -transport ATPases (SERCAs), whereas the Golgi complex depends on both SERCAs and on the much less characterized secretory pathway Ca 2+ -transport ATPases (SPCAs). SPCAs (encoded by ATP2C1 and ATP2C2 in humans) are Golgi-localized pumps that transport both Ca 2+ and Mn 2+ with high affinity. The role of intra-Golgi Ca 2+ /Mn 2+ homeostasis in cellular function and its dependence on SPCAs is discussed, with special emphasis on the expression, catalytic properties, and the link between the defective ATP2C1 gene and Hailey–Hailey disease (HHD) (an autosomal dominant skin disorder).