TgDrpC, an atypical dynamin-related protein in Toxoplasma gondii, is associated with vesicular transport factors and parasite division.

TgDrpC, an atypical dynamin-related protein in Toxoplasma gondii, is associated with vesicular transport factors and parasite division.
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DOI:
10.1111/mmi.14138
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发表时间:
2019-01
影响因子:
3.6
通讯作者:
Arrizabalaga G
Arrizabalaga G
中科院分区:
生物学2区
文献类型:
--
作者:
Heredero-Bermejo I;Varberg JM;Charvat R;Jacobs K;Garbuz T;Sullivan WJ Jr;Arrizabalaga G

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动力蛋白相关蛋白(Dynamin-Related Proteins,DRPs)参与细胞器分裂、囊泡运输等多种过程。弓形虫的胞内寄生虫有三个不同的DRP。TgDrpC的功能仍未解决,它的不同寻常之处在于它缺乏一个保守的GTP酶效应域,这是功能通常所必需的。在这里,我们发现TgDrpC定位于细胞质斑点;然而,在分裂寄生虫时,TgDrpC重新分布到子代细胞的生长边缘。通过条件性基因敲除,我们确定TgDrpC的丢失阻碍了细胞分裂,并导致多细胞器和IMC的迅速恶化。我们还发现TgDrpC与那些与囊泡运输相关的蛋白质相互作用,包括适配器复合体2的成员。其中两个蛋白质,一个是适配器蛋白2(AP-2)复合体亚单位α-1的同源蛋白,另一个是Ezrin-Radisin-moesin(ERM)家族蛋白的同源蛋白,定位于斑点并与子细胞相关。与囊泡运输蛋白的关联一致,TgDrpC在分裂期间重新分配到IMC依赖于高尔基体运输后的情况。综上所述,这些结果支持TgDrpC有助于囊泡运输,并对寄生虫细胞器的稳定和分裂至关重要。
Dynamin-related proteins (Drps) are involved in diverse processes such as organelle division and vesicle trafficking. The intracellular parasite Toxoplasma gondii possesses three distinct Drps. TgDrpC, whose function remains unresolved, is unusual in that it lacks a conserved GTPase Effector Domain, which is typically required for function. Here, we show that TgDrpC localizes to cytoplasmic puncta; however, in dividing parasites, TgDrpC redistributes to the growing edge of the daughter cells. By conditional knockdown, we determined that loss of TgDrpC stalls division and leads to rapid deterioration of multiple organelles and the IMC. We also show that TgDrpC interacts with proteins that exhibit homology to those involved in vesicle transport, including members of the adaptor complex 2. Two of these proteins, a homolog of the adaptor protein 2 (AP-2) complex subunit alpha-1 and a homolog of the ezrin–radixin–moesin (ERM) family proteins, localize to puncta and associate with the daughter cells. Consistent with the association with vesicle transport proteins, re-distribution of TgDrpC to the IMC during division is dependent on post-Golgi trafficking. Together, these results support that TgDrpC contributes to vesicle trafficking and is critical for stability of parasite organelles and division.
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