刚地弓形虫液泡型 H+-ATP 酶调控细胞内 pH 值并影响必需分泌蛋白的成熟。
The Toxoplasma Vacuolar H-ATPase Regulates Intracellular pH and Impacts the Maturation of Essential Secretory Proteins.
机构信息
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602-7400, USA; Department of Microbiology, University of Georgia, Athens, GA 30602-7400, USA.
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602-7400, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602-7400, USA.
出版信息
Cell Rep. 2019 May 14;27(7):2132-2146.e7. doi: 10.1016/j.celrep.2019.04.038.
Vacuolar-proton ATPases (V-ATPases) are conserved complexes that couple the hydrolysis of ATP to the pumping of protons across membranes. V-ATPases are known to play diverse roles in cellular physiology. We studied the Toxoplasma gondii V-ATPase complex and discovered a dual role of the pump in protecting parasites against ionic stress and in the maturation of secretory proteins in endosomal-like compartments. Toxoplasma V-ATPase subunits localize to the plasma membrane and to acidic vesicles, and characterization of conditional mutants of the a1 subunit highlighted the functionality of the complex at both locations. Microneme and rhoptry proteins are required for invasion and modulation of host cells, and they traffic via endosome-like compartments in which proteolytic maturation occurs. We show that the V-ATPase supports the maturation of rhoptry and microneme proteins, and their maturases, during their traffic to their corresponding organelles. This work underscores a role for V-ATPases in regulating virulence pathways.
液泡质子泵 (V-ATPases) 是一种保守的复合物，能够将 ATP 的水解与质子跨膜泵出相结合。V-ATPases 在细胞生理学中具有多种作用。我们研究了刚地弓形虫 V-ATPase 复合物，并发现泵在保护寄生虫免受离子胁迫和在包含体样隔间中分泌蛋白成熟方面具有双重作用。刚地弓形虫 V-ATPase 亚基定位于质膜和酸性小泡上，对 a1 亚基的条件突变体的特征分析突出了该复合物在这两个位置的功能。微线体和棒状体蛋白是入侵和宿主细胞调节所必需的，它们通过包含体样隔间运输，其中发生蛋白水解成熟。我们表明 V-ATPase 支持棒状体和微线体蛋白及其成熟酶在它们到达相应细胞器的过程中的成熟。这项工作强调了 V-ATPases 在调节毒力途径中的作用。
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