Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation.,PLOS Biology

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Loss of MYO5B expression deregulates late endosome size which hinders mitotic spindle orientation.
PLOS Biology ( IF 7.8 ) Pub Date : 2019-11-04 , DOI: 10.1371/journal.pbio.3000531
Changsen Leng ₁ , Arend W Overeem ₁ , Fernando Cartón-Garcia ₂ , Qinghong Li ₁ , Karin Klappe ₁ , Jeroen Kuipers ₁ , Yingying Cui ₃ , Inge S Zuhorn ₄ , Diego Arango ₂ , Sven C D van IJzendoorn ₁

Affiliation

Recycling endosomes regulate plasma membrane recycling. Recently, recycling endosome-associated proteins have been implicated in the positioning and orientation of the mitotic spindle and cytokinesis. Loss of MYO5B, encoding the recycling endosome-associated myosin Vb, is associated with tumor development and tissue architecture defects in the gastrointestinal tract. Whether loss of MYO5B expression affects mitosis is not known. Here, we demonstrate that loss of MYO5B expression delayed cytokinesis, perturbed mitotic spindle orientation, led to the misorientation of the plane of cell division during the course of mitosis, and resulted in the delamination of epithelial cells. Remarkably, the effects on spindle orientation, but not cytokinesis, were a direct consequence of physical hindrance by giant late endosomes, which were formed in a chloride channel-sensitive manner concomitant with a redistribution of chloride channels from the cell periphery to late endosomes upon loss of MYO5B. Rab7 availability was identified as a limiting factor for the development of giant late endosomes. In accordance, increasing rab7 availability corrected mitotic spindle misorientation and cell delamination in cells lacking MYO5B expression. In conclusion, we identified a novel role for MYO5B in the regulation of late endosome size control and identify the inability to control late endosome size as an unexpected novel mechanism underlying defects in cell division orientation and epithelial architecture.

中文翻译：

MYO5B表达的丧失会调节晚期核内体大小，从而阻碍有丝分裂纺锤体定向。

回收内体调节质膜回收。近来，回收与内体相关的蛋白质与有丝分裂纺锤体的定位和定向以及胞质分裂有关。编码回收的内体相关肌球蛋白Vb的MYO5B的丢失与胃肠道中的肿瘤发展和组织结构缺陷有关。MYO5B表达缺失是否影响有丝分裂尚不清楚。在这里，我们证明了MYO5B表达的丧失延迟了细胞分裂，扰动了有丝分裂纺锤体的定向，导致了有丝分裂过程中细胞分裂平面的定向错误，并导致上皮细胞分层。值得注意的是，对纺锤定向的影响（而非胞质分裂）是巨型晚期内体的物理障碍的直接后果，它们以对氯离子通道敏感的方式形成，伴随着MYO5B丢失时氯离子通道从细胞周围到晚期内体的重新分布。Rab7的可用性被确定为巨型晚期内体的发展的限制因素。因此，增加rab7的可用性可纠正缺少MYO5B表达的细胞中的有丝分裂纺锤体定向错误和细胞分层。总之，我们确定了MYO5B在晚期内体大小调控中的新型作用，并确定了无法控制晚期内体大小是作为细胞分裂方向和上皮结构缺陷的基础的意外新机制。Rab7的可用性被确定为巨型晚期内体的发展的限制因素。因此，增加rab7的可用性可纠正缺少MYO5B表达的细胞中的有丝分裂纺锤体定向错误和细胞分层。总之，我们确定了MYO5B在晚期内体大小调控中的新型作用，并确定了无法控制晚期内体大小是作为细胞分裂方向和上皮结构缺陷的基础的意外新机制。Rab7的可用性被确定为巨型晚期内体的发展的限制因素。因此，增加rab7的可用性可纠正缺少MYO5B表达的细胞中的有丝分裂纺锤体定向错误和细胞分层。总之，我们确定了MYO5B在晚期内体大小调控中的新型作用，并确定了无法控制晚期内体大小是作为细胞分裂方向和上皮结构缺陷的基础的意外新机制。

更新日期：2019-12-03

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