Arabiotorre Angela, Formanowicz Megan, Bankaitis Vytas A, Grabon Aby
Department of Cell Biology & Genetics, College of Medicine, Texas A&M Health Sciences Center, College Station, Texas 77843-1114, USA.
Department of Biochemistry & Biophysics, Texas A&M University, College Station, Texas 77843-2128.
bioRxiv. 2023 Jan 9:2023.01.09.523261. doi: 10.1101/2023.01.09.523261.
Phosphoinositide metabolism defines the foundation of a major signaling pathway that is conserved throughout the eukaryotic kingdom. The 4-OH phosphorylated phosphoinositides such as phosphatidylinositol-4-phosphate (PtdIns4P) and phosphatidylinositol-4,5-bisphosphate are particularly important molecules as these execute intrinsically essential activities required for the viability of all eukaryotic cells studied thus far. Using intracellular tachyzoites of the apicomplexan parasite as model for assessing primordial roles for PtdIns4P signaling, we demonstrate the presence of PtdIns4P pools in Golgi/trans-Golgi (TGN) system and in post-TGN compartments of the parasite. Moreover, we show that deficits in PtdIns4P signaling result in structural perturbation of compartments that house dense granule cargo with accompanying deficits in dense granule exocytosis. Taken together, the data report a direct role for PtdIns4P in dense granule biogenesis and exocytosis. The data further indicate that the biogenic pathway for secretion-competent dense granule formation in is more complex than simple budding of fully matured dense granules from the TGN.
磷酸肌醇代谢定义了一条在整个真核生物界保守的主要信号通路的基础。4-羟基磷酸化的磷酸肌醇,如磷脂酰肌醇-4-磷酸(PtdIns4P)和磷脂酰肌醇-4,5-二磷酸,是特别重要的分子,因为它们执行了迄今为止所研究的所有真核细胞生存所需的内在基本活动。利用顶复门寄生虫的细胞内速殖子作为评估PtdIns4P信号通路原始作用的模型,我们证明了PtdIns4P池存在于寄生虫的高尔基体/反式高尔基体(TGN)系统和TGN后区室中。此外,我们表明PtdIns4P信号通路的缺陷会导致容纳致密颗粒货物的区室结构紊乱,并伴随致密颗粒胞吐作用的缺陷。综上所述,这些数据报道了PtdIns4P在致密颗粒生物合成和胞吐作用中的直接作用。数据进一步表明,在[具体生物名称未给出]中具有分泌能力的致密颗粒形成的生物发生途径比从TGN简单出芽完全成熟的致密颗粒更为复杂。