The Role of the Golgi-Resident SPCA Ca2+/Mn2+ Pump in Ionic Homeostasis and Neural Function

Recent evidence highlights the functional importance of the Golgi apparatus (GA) in neurological diseases. The functions of the mammalian GA, in addition to the processing and transport of cargo, also include ionic homeostasis. Besides Ca2+-release channels which serves GA as an agonist-sensitive intracellular Ca2+ store, and Ca2+-binding proteins, the GA contains Ca2+-uptake mechanisms consisting of the well-known sarco-endoplasmic reticulum Ca2+-transport ATPases and the much less characterized secretory-pathway Ca2+-transport ATPases (SPCA). SPCA can transport both Ca2+ and Mn2+ into the Golgi lumen and therefore is involved in the cytosolic and intra-Golgi Ca2+ and Mn2+ homeostasis. It has shown that both of the mRNA and protein of SPCAs are highly expressed in brain. In addition, brain is the region with the highest activity of SPCA isoforms, which may be related to the involvement of Ca2+ and Mn2+ homeostasis in neural functions. In this review, we compile some recent findings showing that the SPCA isoform plays a much more important role in intracellular ionic homeostasis than previously anticipated and illustrating the involvement of SPCA isoforms in certain neurophysiological or neuropathological process. We are interested in gaining insight into the intricate role of the SPCA pumps to explain the GA-specific functions in neurological disorders.