HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
- University of British Columbia, Canada
- Leibniz Institute for Age Research - Fritz Lipmann Institute, Germany
- University of Alberta, Canada
Abstract
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.
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Author details
Christopher A Maxwell
Funding
Canadian Institutes of Health Research (OBC 134038)
- Christopher A Maxwell
Michael Cuccione Foundation
- Marisa Connell
- Helen Chen
- Christopher A Maxwell
Canadian Breast Cancer Foundation
- Tony Chu
Child and Family Research Institute
- Zhengcheng He
- Christopher A Maxwell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures involving animals were in accordance with the Canadian Council on Animal Care (CCAC) and UBC Animal Care Committee (ACC) (Protocol no. A13-0168).
Copyright
© 2017, Connell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
eLife 6:e28672.
https://doi.org/10.7554/eLife.28672
