Format

Send to

Choose Destination
Elife. 2017 Oct 10;6. pii: e28672. doi: 10.7554/eLife.28672.

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

Author information

1
Department of Paediatrics, University of British Columbia, Vancouver, Canada.
2
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
3
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
4
Leibniz Institute on Aging-Fritz Lipmann Institute, Beutenbergstrasse, Germany.
5
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
6
Cross Cancer Institute, Department of Oncology, University of Alberta, Edmonton, Canada.
7
Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital, Vancouver, Canada.
8
Department of Cellular and Physiological Sciences, Life Sciences Centre, University of British Columbia, Vancouver, Canada.
#
Contributed equally

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.

KEYWORDS:

asymmetric cell division; cell biology; developmental biology; human; mouse; neurogenesis; spindle orientation; stem cells

PMID:
28994651
PMCID:
PMC5681225
DOI:
10.7554/eLife.28672
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center