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The RNA-binding protein ATX-2 regulates cytokinesis through PAR-5 and ZEN-4

Megan M Gnazzo1, Eva-Maria E Uhlemann1, Alex R Villarreal1

  • 1Laboratory of Genetics and Medical Genetics, University of Wisconsin-Madison, Madison, WI 53706.

Molecular Biology of the Cell
|August 26, 2016
PubMed

Insights

The RNA-binding protein ATX-2 (Ataxin-2) is crucial for cell division, ensuring proper protein localization at the spindle midzone. This study reveals ATX-2 regulates PAR-5 to maintain ZEN-4, essential for cytokinesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cytokinesis requires precise recruitment of proteins to the spindle midzone.
  • Mechanisms controlling this recruitment, particularly for factors like ZEN-4, are not fully understood.

Purpose of the Study:

  • To elucidate the role of the RNA-binding protein ATX-2 (Ataxin-2) in the spatial and temporal regulation of cell division factors.
  • To investigate how ATX-2 influences the localization of ZEN-4 and PAR-5 during mitosis.

Main Methods:

  • Investigated the function of ATX-2 using genetic manipulation (codepletion).
  • Utilized fluorescent protein tagging (PAR-5-GFP, ZEN-4-GFP) to track protein localization.
  • Analyzed protein levels and localization at mitotic structures like the spindle, centrosomes, and midbody.

Main Results:

  • ATX-2 targets and maintains ZEN-4 at the spindle midzone by regulating PAR-5 levels.
  • Loss of ATX-2 function leads to increased PAR-5 at mitotic structures and decreased ZEN-4 at the spindle midzone.
  • Codepletion of ATX-2 and PAR-5 rescued ZEN-4 localization, indicating ATX-2 acts upstream of PAR-5.

Conclusions:

  • ATX-2 is essential for successful cytokinesis.
  • ATX-2 facilitates ZEN-4 targeting to the spindle midzone via posttranscriptional regulation of PAR-5.
  • This study provides the first direct evidence for ATX-2's necessity in cytokinesis.

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