Akt regulates centrosome migration and spindle orientation in the early Drosophila melanogaster embryo

Graham J Buttrick1, Luke M A Beaumont, Jessica Leitch

  • 1Department of Zoology, University of Oxford, Oxford OX1 3PS, England, UK.

The Journal of Cell Biology
|February 13, 2008
PubMed

Insights

The protein kinase Akt is crucial for proper cell division in fruit fly embryos. Reduced Akt levels disrupt mitotic spindle positioning, leading to nuclear abnormalities and cell shape defects.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • Correct positioning and morphology of the mitotic spindle are essential for accurate cell division.
  • Microtubule (MT)-cortical actin interactions regulate mitotic spindle organization.
  • Disruptions in these processes can lead to developmental abnormalities.

Purpose of the Study:

  • To investigate the role of the protein kinase Akt in regulating mitotic spindle positioning and orientation in the early Drosophila melanogaster embryo.
  • To identify downstream targets and interacting partners of Akt involved in this process.

Main Methods:

  • Used Drosophila melanogaster early embryos with reduced levels of the protein kinase Akt.
  • Assessed centrosome migration, mitotic spindle morphology, and nuclear positioning.
  • Investigated the phosphorylation status of Zw3 and the cortical localization of APC2 and EB1.
  • Examined mitotic spindle orientation in postcellularized embryos.

Main Results:

  • Reduced Akt levels caused incomplete centrosome migration, bent mitotic spindles, and nuclear loss.
  • Akt is enriched at the embryonic cortex and is required for Zw3 phosphorylation.
  • Akt regulates the cortical localization of APC2 and the MT + Tip protein EB1.
  • Akt reduction led to APC2 mislocalization and mitotic spindle misorientation.

Conclusions:

  • Akt plays a critical role in stabilizing microtubule-cortex interactions during early embryonic development.
  • Akt regulates a complex involving Zw3, Armadillo, APC2, and EB1.
  • This Akt-mediated complex is essential for proper centrosome separation and mitotic spindle orientation.

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