De Loof Arnold, Schoofs Liliane
Research Group of Functional Genomics and Proteomics, Department of Biology, KU Leuven, Leuven, Belgium.
Front Physiol. 2020 Oct 15;11:542879. doi: 10.3389/fphys.2020.542879. eCollection 2020.
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.
大量关于高尔基体系统的文献强调了其在蛋白质分泌和修饰中的作用，通常未明确这种分泌源于何种进化古老的细胞生理需求。也未明确分泌蛋白必须满足哪些功能要求。通过对一些主要（但不限于）从（昆虫）内分泌学获得的经典和最新数据进行重新解读，出现了一种观点，即所有真核生物中粗面内质网（RER）-高尔基体复合体的可能原始功能不是分泌任何类型的蛋白质，而是从细胞质中去除有毒的过量钙。这种活动需要同时分泌大量作为RER-高尔基体内部微传送带系统的载钙/转运蛋白。因此，（增加适应性的）蛋白质分泌从属于钙的去除。牛奶中蛋白质和钙含量很高（60 - 90 mM，而未受刺激的乳腺细胞中为100 nM）就是一个极端例子。肌（内）质网钙ATP酶（SERCAs）和SPCA1a钙/锰转运ATP酶是通过高尔基体进行钙去除的主要参与者。两者都被倍半萜类毒胡萝卜素阻断。这强化了（2014年的）假设，即内源性法尼醇样倍半萜类化合物（FLSs）可能是内质网和高尔基体中长期寻找但仍未确定的钙泵的作用物质。第二个假定功能也出现了。进入和离开的运输小泡分别在高尔基体堆栈的顺面和反面与膜系统融合，这需要所涉及的膜具有高度灵活性和快速自我封闭性。这些特性可能 - 可能部分地 - 由内源性疏水膜“流化剂”控制，而FLSs是主要候选物质。最近对未解释的经典数据的重新审视表明，它们可能是由高尔基体自身合成的。这个改变游戏规则的假设得到了一些论据和数据的支持，其中一些可追溯到1964年，即昆虫咽侧体（CA）作为法尼醇酯的主要产生部位，具有活跃的高尔基体系统。因此，除了分泌FLS，特别是保幼激素外，它还分泌一种或多种功能迄今未知的蛋白质或肽。本文提出了细胞生理学和普通内分泌学中各种未解决问题的答案。
