HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development

Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centro...

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Bibliographic Details
Main Authors: Marisa Connell, Helen Chen, Jihong Jiang, Chia-Wei Kuan, Abbas Fotovati, Tony LH Chu, Zhengcheng He, Tess C Lengyell, Huaibiao Li, Torsten Kroll, Amanda M Li, Daniel Goldowitz, Lucien Frappart, Aspasia Ploubidou, Millan S Patel, Linda M Pilarski, Elizabeth M Simpson, Philipp F Lange, Douglas W Allan, Christopher A Maxwell
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-10-01
Series:eLife
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Online Access:https://elifesciences.org/articles/28672
Description
Summary:Oriented cell division is one mechanism progenitor cells use during development and to maintain tissue homeostasis. Common to most cell types is the asymmetric establishment and regulation of cortical NuMA-dynein complexes that position the mitotic spindle. Here, we discover that HMMR acts at centrosomes in a PLK1-dependent pathway that locates active Ran and modulates the cortical localization of NuMA-dynein complexes to correct mispositioned spindles. This pathway was discovered through the creation and analysis of Hmmr-knockout mice, which suffer neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues. HMMR over-expression in immortalized cancer cells induces phenotypes consistent with an increase in active Ran including defects in spindle orientation. These data identify an essential role for HMMR in the PLK1-dependent regulatory pathway that orients progenitor cell division and supports neural development.
ISSN:2050-084X