Andrea Hutterer1, Daniela Berdnik2,3,
Alex Schleiffer2, Juergen A. Knoblich1. 1)
Institute of Molecular Biotechnology (IMBA), Vienna, Austria; 2)
Institute of Molecular Pathology (IMP), Vienna, Austria; 3)
Department of Biological Sciences, Stanford University, Stanford,
CA.
During asymmetric cell division of precursor cells of the
Drosophila peripheral nervous system the protein Numb is
segregated into only one of the two daughter cells where it induces
a particular developmental fate. Asymmetric Numb localization as
well as centrosome maturation require the activity of the mitotic
kinase Aurora-A. How Aurora-A
is activated at the onset of mitosis is not clear yet.
In a screen for genes involved in asymmetric cell division we have
identified the novel gene borealis (bora). bora
mutants have identical phenotypes to auroraA mutants. Numb
fails to localize asymmetrically and centrosome maturation is
impaired. Genetic and biochemical experiments show a close
functional connection between Bora and Aurora-A.
Overexpression of bora can rescue the defects caused by
mutations in auroraA. Bora is conserved in vertebrates and
both Drosophila and human Bora can bind to Aurora-A
and activate the kinase in vitro. Bora shows a striking
subcellular localization: In interphase cells, Bora is a nuclear
protein but upon entry into mitosis, Bora is excluded from the
nucleus and translocates into the cytoplasm in a Cdc2 dependent
manner. Additionally Cdc2 can phosphorylate Bora in vitro.
We propose a model in which activation of Cdc2 initiates the release
of Bora into the cytoplasm where it can bind to and activate
Aurora-A. |