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Dictyostelium lacking the single atlastin homolog Sey1 shows aberrant ER architecture, proteolytic processes and expansion of the Legionella‐containing vacuole
Cellular Microbiology ( IF 2.6 ) Pub Date : 2021-02-14 , DOI: 10.1111/cmi.13318
Dario Hüsler 1 , Bernhard Steiner 1 , Amanda Welin 2 , Bianca Striednig 1 , A Leoni Swart 1 , Virginie Molle 3 , Hubert Hilbi 1 , François Letourneur 3
Affiliation  

Dictyostelium discoideum Sey1 is the single ortholog of mammalian atlastin 1–3 (ATL1‐3), which are large homodimeric GTPases mediating homotypic fusion of endoplasmic reticulum (ER) tubules. In this study, we generated a D. discoideum mutant strain lacking the sey1 gene and found that amoebae deleted for sey1 are enlarged, but grow and develop similarly to the parental strain. The ∆sey1 mutant amoebae showed an altered ER architecture, and the tubular ER network was partially disrupted without any major consequences for other organelles or the architecture of the secretory and endocytic pathways. Macropinocytic and phagocytic functions were preserved; however, the mutant amoebae exhibited cumulative defects in lysosomal enzymes exocytosis, intracellular proteolysis, and cell motility, resulting in impaired growth on bacterial lawns. Moreover, ∆sey1 mutant cells showed a constitutive activation of the unfolded protein response pathway (UPR), but they still readily adapted to moderate levels of ER stress, while unable to cope with prolonged stress. In D. discoideumsey1 the formation of the ER‐associated compartment harbouring the bacterial pathogen Legionella pneumophila was also impaired. In the mutant amoebae, the ER was less efficiently recruited to the “Legionella‐containing vacuole” (LCV), the expansion of the pathogen vacuole was inhibited at early stages of infection and intracellular bacterial growth was reduced. In summary, our study establishes a role of D. discoideum Sey1 in ER architecture, proteolysis, cell motility and intracellular replication of L. pneumophila.

中文翻译:

缺乏单个 atlastin 同源物 Sey1 的网柄菌表现出异常的 ER 结构、蛋白水解过程和含军团菌的液泡的扩张

盘基网柄菌Sey1 是哺乳动物 atlastin 1-3 (ATL1-3) 的单一直向同源物,ATL1-3 是介导内质网 (ER) 小管同型融合的大型同源二聚体 GTP 酶。在这项研究中,我们产生了D.菌缺乏突变株sey1基因,并发现该变形虫删除sey1被放大,但与亲本菌株成长和发展与此类似。Δ sey1突变的变形虫显示出改变的 ER 结构,管状 ER 网络被部分破坏,对其他细胞器或分泌和内吞途径的结构没有任何重大影响。巨胞饮和吞噬功能得以保留;然而,突变的变形虫在溶酶体酶胞吐作用、细胞内蛋白水解和细胞运动方面表现出累积缺陷,导致细菌草坪的生长受损。此外,Δ sey1突变细胞表现出未折叠蛋白反应途径(UPR)的组成型激活,但它们仍然很容易适应中等水平的内质网应激,同时无法应对长时间的应激。在D. discoideumsey1携带细菌病原体嗜肺军团菌的内质网相关隔室的形成也受到损害。在突变的变形虫中,ER 被较少有效地募集到“含军团菌的液泡”(LCV)中,病原体液泡的扩张在感染早期受到抑制,细胞内细菌生长减少。总之,我们的研究确定了D. discoideum Sey1 在嗜肺军团菌的ER 结构、蛋白水解、细胞运动和细胞内复制中的作用。
更新日期:2021-04-12
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