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 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.

• Publication year

  2017

• Venue

  eLife

• Publication date

  2017-09-10

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.7554/eLife.28672PMID 28994651PMCID 5681225
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• HMMR over-expression in immortalized cancer cells induces phenotypes consistent with increased active Ran, including defects in spindle orientation.

  Confidence 0.94

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• Hmmr-knockout mice exhibit neonatal lethality with defective neural development and pleiotropic phenotypes in multiple tissues.

  Confidence 0.96

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• HMMR acts at centrosomes in a PLK1-dependent pathway that localizes active Ran and modulates cortical NuMA-dynein complexes to correct mispositioned spindles.

  Confidence 0.98

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

• active ran

  molecule

  The activated Ran pool referenced as a regulator of spindle-positioning machinery.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• centrosomes

  organelle

  Microtubule-organizing structures that serve as the subcellular site where HMMR acts in this pathway.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• hmmr

  protein

  A centrosome-associated protein examined for its role in the spindle-positioning pathway.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• hmmr-knockout mice

  model organism

  Mice engineered to lack Hmmr and used to assess HMMR function in vivo.

  Aliases: HMMR knockout mice

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• immortalized cancer cells

  cell line

  Cultured transformed cells used for HMMR over-expression experiments.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• neural development

  developmental process

  The development of nervous system tissues evaluated for defects in the knockout mouse model.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• numa-dynein complexes

  protein complex

  Cortical motor-adaptor complexes that position the mitotic spindle at the cell cortex.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• plk1-dependent pathway

  pathway

  A signaling route that requires PLK1 and links centrosomal regulation to spindle-positioning control.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• spindle orientation

  cellular process

  The alignment and positioning of the mitotic spindle during cell division.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

• Division

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