Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection.
Microtubules and Dynein Regulate Human Neutrophil Nuclear Volume and Hypersegmentation During H. pylori Infection.
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DOI：
10.3389/fimmu.2021.653100
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发表时间：
2021
影响因子：
7.3
通讯作者：
Allen LH
中科院分区：
文献类型：
--
作者：
Silva-Del Toro SL;Allen LH
中性粒细胞（也称为多形核白细胞，pmn）是异质的，可以表现出相当大的表型和功能可塑性。与此一致，我们先前发现幽门螺杆菌感染诱导人类PMNs的n1样亚型分化，其显著的核超分割。在这里，我们利用生化方法和共聚焦和超分辨率显微镜来深入了解潜在的分子机制。对诺可达唑和紫杉醇抑制的敏感性表明，微管动力学是诱导和维持超分割的必要条件，超分辨率受激辐射耗竭（STED）成像显示，在超分割的细胞中，微管明显更丰富、更长。动力蛋白的活性也是必需的，在幽门螺杆菌感染后，这种动力蛋白在核周围的富集增强。相比之下，中心体没有发生分裂，层粘连蛋白B受体丰度和内质网形态没有变化。最后，使用Imaris软件对STED图像堆进行分析，发现核体积在超分割开始前显著增加，并且在有无感染的情况下，诺可达唑和紫杉醇对核大小的调节是不同的。综上所述，我们的数据定义了一种由微管和动力蛋白介导的超分割的新机制，并因此推进了对调节核形态过程的理解。
Neutrophils (also called polymorphonuclear leukocytes, PMNs) are heterogeneous and can exhibit considerable phenotypic and functional plasticity. In keeping with this, we discovered previously that Helicobacter pylori infection induces N1-like subtype differentiation of human PMNs that is notable for profound nuclear hypersegmentation. Herein, we utilized biochemical approaches and confocal and super-resolution microscopy to gain insight into the underlying molecular mechanisms. Sensitivity to inhibition by nocodazole and taxol indicated that microtubule dynamics were required to induce and sustain hypersegmentation, and super-resolution Stimulated Emission Depletion (STED) imaging demonstrated that microtubules were significantly more abundant and longer in hypersegmented cells. Dynein activity was also required, and enrichment of this motor protein at the nuclear periphery was enhanced following H. pylori infection. In contrast, centrosome splitting did not occur, and lamin B receptor abundance and ER morphology were unchanged. Finally, analysis of STED image stacks using Imaris software revealed that nuclear volume increased markedly prior to the onset of hypersegmentation and that nuclear size was differentially modulated by nocodazole and taxol in the presence and absence of infection. Taken together, our data define a new mechanism of hypersegmentation that is mediated by microtubules and dynein and as such advance understanding of processes that regulate nuclear morphology.
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DOI：
10.1084/jem.191.1.115
发表时间：
2000-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Allen LA;Schlesinger LS;Kang B
通讯作者：
Kang B
影响因子：
8
作者：
Gerlitz, Gabi;Reiner, Orly;Bustin, Michael
通讯作者：
Bustin, Michael
肌动球蛋白和波形蛋白细胞骨架网络调节核形状、力学和染色质组织。
影响因子：
4.6
作者：
Keeling MC;Flores LR;Dodhy AH;Murray ER;Gavara N
通讯作者：
Gavara N
影响因子：
2.9
作者：
Lokwani, Ravi;Wark, Peter A. B.;Simpson, Jodie L.
通讯作者：
Simpson, Jodie L.
影响因子：
6
作者：
Doolin, Mary T.;Ornstein, Thea S.;Stroka, Kimberly M.
通讯作者：
Stroka, Kimberly M.