Abstract
The Golgi apparatus (GA) is a bona fide Ca2+ store; however, there is a lack of GA-specific Ca2+ mobilizing agents. Here, we report that emetine specifically releases Ca2+ from GA in HeLa and HL-1 atrial myocytes. Additionally, it has become evident that the trans-Golgi is a labile Ca2+ store that requires a continuous source of Ca2+ from either the external milieu or from the ER, to enable it to produce a detectable transient increase in cytosolic Ca2+. Our data indicates that the emetine-sensitive Ca2+ mobilizing mechanism is different from the two classical Ca2+ release mechanisms, i.e. IP3 and ryanodine receptors. This newly discovered ability of emetine to release Ca2+ from the GA may explain why chronic consumption of ipecac syrup has muscle side effects.
Highlights
A tight control of cellular Ca2+ homeostasis is a typical characteristic of all eukaryotes
While using emetine to study the well-established role of Sec[61] translocon in the endoplasmic reticulum (ER) Ca2+ leak[23], we found that this alkaloid, which is present in ipecac syrup[24], was able to reduce the Ca2+ content of an undefined Ca2+ store in HeLa cells
In the presence of external [Ca2+], the combination of Adenosine triphosphate (ATP) and thapsigargin (Tg, an irreversible sarco/endoplasmic reticulum Ca2+-ATPases (SERCA) pump inhibitor) induced a transient increase in the [Ca2+]c and this was associated with a sustained reduction in the [Ca2+]L signal (Fig. 1A, black trace)
Summary
A tight control of cellular Ca2+ homeostasis is a typical characteristic of all eukaryotes. Cells are equipped with a complex Ca2+ toolkit, which enables them to maintain cytosolic Ca2+ concentrations ([Ca2+]c) at a very low level (~100 nM) This is achieved by the concerted action of Ca2+ extrusion mechanisms localized in the plasma membrane (PM), Ca2+ storage within the lumen of intracellular compartments, and is facilitated by Ca2+ buffering proteins within the cytosol and organelle lumen[1]. Regarding Ca2+ control within cellular organelles, the endoplasmic reticulum (ER), or its specialized version in muscle cells called the sarcoplasmic reticulum (SR), represents the most abundant storage compartment It possesses a well characterized ATP-dependent Ca2+ accumulation mechanisms, the sarco/endoplasmic reticulum Ca2+-ATPases (SERCA), as well as two Ca2+ release channels; the inositol trisphosphate (IP3) receptors (IP3R) and/or the ryanodine receptors (RyR)[4,5]. Emetine may represent the first member of a chemical library that will enable studies on the mechanism of GA Ca2+ homeostasis and its role in Ca2+ pathophysiology
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