Two Undervalued Functions of the Golgi Apparatus: Removal of Excess Ca2+ and Biosynthesis of Farnesol-Like Sesquiterpenoids, Possibly as Ca2+-Pump Agonists and Membrane “Fluidizers–Plasticizers”

Abstract

The extensive literature dealing with the Golgi system emphasizes its role in protein secretion and modification, usually without specifying from which evolutionary ancient cell physiological necessity such secretion originated. Neither does it specify which functional requirements the secreted proteins must meet. From a reinterpretation of some classical and recent data gained mainly, but not exclusively, from (insect) endocrinology, the view emerged that the likely primordial function of the rough endoplasmic reticulum (RER)-Golgi complex in all eukaryotes was not the secretion of any type of protein but the removal of toxic excess Ca 2+ from the cytoplasm. Such activity requires the concurrent secretion of large amounts of Ca 2+-carrying/transporting proteins acting as a micro-conveyor belt system inside the RER-Golgi. Thus, (fitness increasing) protein secretion is subordinate to Ca 2+ removal. Milk with its high content of protein and Ca 2+ (60-90 mM vs. 100 nM in unstimulated mammary gland cells) is an extreme example. The sarco(endo)plasmatic reticulum Ca 2+-ATPases (SERCAs) and SPCA1a Ca 2+ /Mn 2+ transport ATPases are major players in Ca 2+ removal through the Golgi. Both are blocked by the sesquiterpenoid thapsigargin. This strengthens the hypothesis (2014) that endogenous farnesol-like sesquiterpenoids (FLSs) may act as the long sought for but still unidentified agonist(s) for Ca 2+-pumps in both the ER and Golgi. A second putative function also emerges. The fusion of both the incoming and outgoing transport vesicles, respectively, at the cis-and trans-side of Golgi stacks, with the membrane system requiring high flexibility and fast self-closing of the involved membranes. These properties may-possibly partially-be controlled by endogenous hydrophobic membrane "fluidizers" for which FLSs are prime candidates. A recent reexamination of unexplained classical data suggests that they are likely synthesized by the Golgi itself. This game-changing hypothesis is endorsed by several arguments and data, some of which date from 1964, that the insect corpus allatum (CA), which is the major production site of farnesol-esters, has active Golgi systems. Thus, in addition to

MiR‐3017b contributes to metamorphosis by targeting sarco/endoplasmic reticulum Ca2+ATPase in Tribolium castaneum

“…We next examined the underlying mechanism of this function. As a Calcium ion pump, SERCA is responsible for calcium homeostasis by storing calcium in Sarco/endoplasmic reticulum (ER) under 20E action, which activates the downstream responsive genes of 20E and initiates metamorphosis (De Loof & Schoofs, 2020; Liu et al, 2014; Wang et al, 2016). To evaluate the correlation between 20E and miRNA‐3017b ‐ SERCA , exogenous 20E was applied to day‐one sixth instar larvae of T. castaneum to evaluate the expression level of miR‐3017b and SERCA .…”

A New Antiport Mechanism Using the Abnormal Adsorption of Ions

“…Ion pumps are an intriguing and perennial subject in scientific research due to their significant involvement in life processes and potential applications in various fields, such as molecular motors, water desalination, and ion batteries. − When compared to the ion pumps in nonbiological systems, which are simply driven by an external electrical potential, those in biological systems are of much greater interest, as they have delicate mechanisms and high efficiencies. Three of the most famous ion pumps in biological systems are the Na + /K + pump, Ca 2+ pump, and proton pump, and these provide typical examples of active transport. − …”