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A Highlights from MBoC Selection: Genetically induced microtubule disruption in the mouse intestine impairs intracellular organization and transport

机译:MBoC选择的亮点:小鼠肠道中遗传诱导的微管破坏会破坏细胞内的组织和运输

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摘要

In most differentiated cells, microtubules reorganize into noncentrosomal arrays that are cell-type specific. In the columnar absorptive enterocytes of the intestine, microtubules form polarized apical–basal arrays that have been proposed to play multiple roles. However, in vivo testing of these hypotheses has been hampered by a lack of genetic tools to specifically perturb microtubules. Here we analyze mice in which microtubules are disrupted by conditional inducible expression of the microtubule-severing protein spastin. Spastin overexpression resulted in multiple cellular defects, including aberrations in nuclear and organelle positioning and deficient nutrient transport. However, cell shape, adhesion, and polarity remained intact, and mutant mice continued to thrive. Notably, the phenotypes of microtubule disruption are similar to those induced by microtubule disorganization upon loss of CAMSAP3/Nezha. These data demonstrate that enterocyte microtubules have important roles in organelle organization but are not essential for growth under homeostatic conditions.
机译:在大多数分化的细胞中,微管会重组为细胞类型特异性的非中心体阵列。在小肠的柱状吸收性肠上皮细胞中,微管形成极化的顶基-基底阵列,已提出它们起多种作用。但是,由于缺乏专门干扰微管的遗传工具,这些假设的体内测试受到了阻碍。在这里,我们分析了通过微管切断蛋白spastin的条件诱导表达来破坏微管的小鼠。 Spastin的过表达导致多种细胞缺陷,包括核和细胞器定位的异常以及营养物质的运输不足。但是,细胞的形状,粘附性和极性仍保持不变,并且突变小鼠继续存活。值得注意的是,微管破坏的表型类似于在失去CAMSAP3 / Nezha时由微管解体诱导的表型。这些数据表明肠上皮细胞微管在细胞器组织中具有重要作用,但对于稳态条件下的生长并不是必需的。

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