GSK3β mediates acentromeric spindle stabilization by activated PKCζ

Research output: Contribution to journalArticle

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Abstract

Upon fertilization, the mammalian egg undergoes a precise series of signaling events that orchestrate its conversion into a zygote. Mouse eggs contain acentrosomal spindle poles when arrested at meiotic metaphase II. The meiotic spindle is thought to provide a scaffold that mediates spatial and temporal regulation of the signaling pathways orchestrating post-fertilization events. Many kinases have been found to be enriched at the MII meiotic spindle, such as Protein Kinase C (PKC), and are thought to have an important role in regulating signaling events initiated through fertilization. In this study phosphorylated PKCζ (p-PKCζ) and Glycogen Synthase Kinase 3β (GSK3β) were found to be enriched at both acentrosomal spindle poles and the kinetochore region. Phosphorylated PKCζ (p-PKCζ) was immunopurified from MII eggs and was found to co-localize with known microtubule stabilizing components found in somatic cells, including GSK3β and Partition deficit protein 6 (Par6). Both fluorescence resonance energy transfer (FRET) and immunofluorescence confirmed the existence and close association of these proteins with p-PKCζ at the meiotic spindle. When GSK3β is phosphorylated on ser9 its activity is inhibited and the spindle is stabilized. However, when GSK3β is dephosphorylated (on ser9) it becomes active and the spindle is destabilized. The mechanism by which p-PKCζ maintains spindle organization appears to be through GSK3β and suggests that p-PKCζ phosphorylates GSK3β on the ser9 position inactivating GSK3β and consequently maintaining spindle stability during meiotic metaphase arrest.

Original languageEnglish (US)
Pages (from-to)46-58
Number of pages13
JournalDevelopmental Biology
Volume317
Issue number1
DOIs
StatePublished - May 1 2008

Fingerprint

Glycogen Synthase Kinase 3
Protein Kinase C
Spindle Apparatus
Fertilization
Spindle Poles
Metaphase
Eggs
Kinetochores
Fluorescence Resonance Energy Transfer
Zygote
Microtubules
Fluorescent Antibody Technique
Ovum
Proteins
Phosphotransferases

Keywords

  • Egg
  • Fertilization
  • GSK
  • PKC
  • Scaffold
  • Signal transduction

ASJC Scopus subject areas

  • Developmental Biology

Cite this

GSK3β mediates acentromeric spindle stabilization by activated PKCζ. / Baluch, Debra; Capco, David.

In: Developmental Biology, Vol. 317, No. 1, 01.05.2008, p. 46-58.

Research output: Contribution to journalArticle

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