The SPCA1 Ca2+ Pump and Intracellular Membrane Trafficking

Abstract

The Golgi apparatus (GA) is a dynamic store of Ca 2+ that can be released into the cell cytosol. It can thus participate in the regulation of the Ca 2+ concentration in the cytosol ([Ca 2+ ] cyt ), which might be critical for intra-Golgi transport. Secretory pathway Ca 2+ -ATPase pump type 1 (SPCA1) is important in Golgi homeostasis of Ca 2+ . The subcellular localization of SPCA1 appears to be GA specific, although its precise location within the GA is not known. Here, we show that SPCA1 is mostly excluded from the cores of the Golgi cisternae and is instead located mainly on the lateral rims of Golgi stacks, in tubular noncompact zones that interconnect different Golgi stacks, and within tubular parts of the trans Golgi network, suggesting a role in regulation of the local [Ca 2+ ] cyt that is crucial for membrane fusion. SPCA1 knockdown by RNA interference induces GA fragmentation. These Golgi fragments lack the cismost and trans-most cisternae and remain within the perinuclear region. This SPCA1 knockdown inhibits exit of vesicular stomatitis virus G-protein from the GA and delays retrograde redistribution of the GA glycosylation enzymes into the endoplasmic reticulum caused by brefeldin A; however, exit of these enzymes from the endoplasmic reticulum is not affected. Thus, correct SPCA1 functioning is crucial to intra-Golgi transport and maintenance of the Golgi ribbon.

The Role of Calcium in Intracellular Trafficking

“…However, this is in contrast with previous report where a SPCA1-/-murine model present normal secretion, with a lethal phenotype [98]. In all these recent reports, where the [Ca 2+ ] GA is altered by the SPCA1 depletion, the GA is drastically degenerated or fragmented [95][96][97][98]. This highlights the critical role of the correct [Ca 2+ ] GA homeostasis in maintenance of GA morphology.…”

“…2B-D) and the fundamental role in protein trafficking played by cPLA2 has been reported [94]. Most recently has been reported that the lack of SPCA1 impaired Golgi Ca 2+ homeostasis and resulted in disturbed trafficking of different classes of proteins including normally Golgilocalized [95], with a delay of the correct secretion of the VSVG in human cells [96,97]. However, this is in contrast with previous report where a SPCA1-/-murine model present normal secretion, with a lethal phenotype [98].…”

Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread

“…Similar genes were recently identified in host factor screens for dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV) and Rift Valley fever virus (Marceau et al, 2016; Riblett et al, 2016; Savidis et al, 2016; Zhang et al, 2016). We also identified SPCA1, a secretory pathway calcium (Ca 2+ ) transport ATPase encoded by ATP2C1 (Figure 1B) that facilitates Ca 2+ and Mn 2+ uptake into the trans -Golgi network (TGN) (Behne et al, 2003; Lissandron et al, 2010; Micaroni et al, 2010). The TGN is rich in enzymes (e.g.…”

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

“…Fluorescence microscopy of the endogenously expressed SPCA1 in many cell lines [28][29][30] also revealed a Golgi-like distribution and probably a expression pattern of more distal parts of the secretory pathway [31]. As for which subcompartment of the Golgi expresses this pump is still not very clear [32,33], and it seems to be mainly localized in the trans-Golgi.…”

“…Furthermore, the latest research revealed that the precise location of SPCA1 within the GA was mainly on the lateral rims of Golgi stacks, in tubular noncompact zones that interconnect different Golgi stacks, and within tubular parts of the trans Golgi network, suggesting a role in regulation of the local [Ca 2? ] cyt that is crucial for membrane fusion [32]. Ca 2?…”