高尔基体和内质网对刚地弓形虫钙和pH稳态的作用。

The contribution of the Golgi and the endoplasmic reticulum to calcium and pH homeostasis in Toxoplasma gondii.

作者信息

Calixto Abigail, Moen Katherine E, Moreno Silvia N J

机构信息

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA; Department of Microbiology, University of Georgia, Athens, Georgia, USA.

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA; Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.

出版信息

J Biol Chem. 2025 Apr;301(4):108372. doi: 10.1016/j.jbc.2025.108372. Epub 2025 Mar 3.

DOI:10.1016/j.jbc.2025.108372

PMID:40043955

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12131190/

Abstract

The cytosolic Ca concentration of all cells is highly regulated demanding the coordinated operation of Ca pumps, channels, exchangers, and binding proteins. In the protozoan parasite Toxoplasma gondii, calcium homeostasis, essential for signaling, governs critical virulence traits. However, the identity of most molecular players involved in signaling and homeostasis in T. gondii is unknown or poorly characterized. In this work, we studied a putative calcium proton exchanger, TgGT1_319550 (TgCAXL1), which belongs to a family of Ca/proton exchangers that localize to the Golgi apparatus. We localized TgCAXL1 to the Golgi and the endoplasmic reticulum (ER) of T. gondii and validated its role as a Ca/proton exchanger by yeast complementation. Characterization of a knock-out mutant for TgCAXL1 (Δcaxl) underscored the role of TgCAXL1 in Ca storage by the ER and acidic stores, most likely the Golgi. Most interestingly, TgCAXL1 function is linked to the Ca pumping activity of the Sarcoendoplasmic Reticulum Ca-ATPase (TgSERCA). TgCAXL1 functions in cytosolic pH regulation and recovery from acidic stress. Our data showed for the first time the role of the Golgi in storing and modulating Ca signaling in T. gondii and the potential link between pH regulation and TgSERCA activity, which is essential for filling intracellular stores with Ca.

摘要

所有细胞的胞质钙浓度都受到高度调节，这需要钙泵、通道、交换体和结合蛋白的协同运作。在原生动物寄生虫弓形虫中，对信号传导至关重要的钙稳态控制着关键的毒力特征。然而，参与弓形虫信号传导和稳态的大多数分子成分的身份尚不清楚或特征描述不足。在这项研究中，我们研究了一种假定的钙质子交换体TgGT1_319550（TgCAXL1），它属于定位于高尔基体的钙/质子交换体家族。我们将TgCAXL1定位于弓形虫的高尔基体和内质网（ER），并通过酵母互补验证了其作为钙/质子交换体的作用。对TgCAXL1基因敲除突变体（Δcaxl）的表征强调了TgCAXL1在内质网和酸性储存库（很可能是高尔基体）钙储存中的作用。最有趣的是，TgCAXL1的功能与肌浆内质网钙ATP酶（TgSERCA）的钙泵活性有关。TgCAXL1在细胞质pH调节和从酸性应激中恢复方面发挥作用。我们的数据首次显示了高尔基体在弓形虫钙信号储存和调节中的作用，以及pH调节与TgSERCA活性之间的潜在联系，而TgSERCA活性对于用钙填充细胞内储存库至关重要。