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Related Experiment Videos

Subcellular translocation signals regulate Geminin activity during embryonic development.

Aline Boos1, Amy Lee, Dominic M Thompson

  • 1Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.

Biology of the Cell
|February 9, 2006
PubMed
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Geminin protein

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Background:

  • Geminin (Gem) is crucial for DNA replication fidelity and embryonic cell fate.
  • Gem's primary location is the nucleus during the cell cycle.
  • Nuclear import regulates Gem activation in certain contexts.

Purpose of the Study:

  • Define structural and mechanistic features of Gem's subcellular localization.
  • Investigate the impact of Gem's subcellular localization on cell fate specification.

Main Methods:

  • Determined the bipartite nuclear localization signal (NLS) in Xenopus Gem.
  • Used microinjection in Xenopus embryos to test import-deficient Gem.
  • Performed cross-species sequence comparison of Gem proteins.

Related Experiment Videos

  • Identified alternative N-terminal motifs in human Gem.
  • Investigated Crm1-dependent nuclear export and Cdt1-mediated import.

    • Main Results:

    • Nuclear import of Xenopus Gem relies on an N-terminal bipartite NLS.
    • Import-deficient Gem failed to modulate ectodermal cell fate; rescue by heterologous NLS.
    • Xenopus NLS is conserved in non-mammalian vertebrates but not mammals.
    • Human Gem uses a different N-terminal motif for nuclear localization.
    • Crm1-mediated export and Cdt1-mediated import also regulate Gem localization.

    Conclusions:

    • Gem's cell fate and cell-cycle regulatory activities depend on controlled subcellular localization.
    • Gem likely shuttles between nucleus and cytoplasm via multiple mechanisms.
    • Stringent control of Gem localization is essential for cell-cycle progression and development.