Two Undervalued Functions of the Golgi Apparatus: Removal of Excess Ca and Biosynthesis of Farnesol-Like Sesquiterpenoids, Possibly as Ca-Pump Agonists and Membrane "Fluidizers-Plasticizers".

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 from the cytoplasm. Such activity requires the concurrent secretion of large amounts of Ca-carrying/transporting proteins acting as a micro-conveyor belt system inside the RER-Golgi. Thus, (fitness increasing) protein secretion is subordinate to Ca removal. Milk with its high content of protein and Ca (60-90 mM vs. 100 nM in unstimulated mammary gland cells) is an extreme example. The sarco(endo)plasmatic reticulum Ca-ATPases (SERCAs) and SPCA1a Ca/Mn transport ATPases are major players in Ca 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 (s) for Ca-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 - and - 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 (CA), which is the major production site of farnesol-esters, has active Golgi systems. Thus, in addition to secreting FLS, in particular juvenile hormone(s), it also secretes a protein(s) or peptide(s) with thus far unknown function. This paper suggests answers to various open questions in cell physiology and general endocrinology.