It had previously been established that asymmetric cell division is extremely important in determining cell fates. Asymmetric cell division occurs when a molecule is inherited by only one of the two cells that arise following cell division (mitosis).
It was established well over a decade ago that in the sensory organ precursor cells (SOP cells) of the fruit fly Drosophila melanogaster the "Numb" protein is segregated into only one of the two daughter cells. How this takes place, however, has remained a matter of conjecture despite the intense efforts of at least 10 groups worldwide.
Knoblich was one of the scientists involved in the early characterization of the molecules involved in Numb's asymmetric localization and he has continued to study the mechanism from his early post-doc days to the present. Some time ago he and others showed that the protein "Lethal giant larvae" (Lgl) and an atypical protein kinase C (aPKC) were involved but scientists were unable to say how the phosphorylation of Lgl by aPKC affected Numb's localization.
The facilities at the IMBA and the adjoining Institute for Molecular Pathology (IMP) have enabled a wide range of methods to be brought to bear on the problem. Key to Knoblich's work has been a recently developed method for imaging live flies. Knoblich has been studying Numb localization by means of a uniquely multidisciplinary approach, combining live imaging methods with genetics and biochemistry. The kinase AuroraA (Aur-A) was known to be activated at the start of cell division and to be required for Numb activity. Knoblich has now shown that AurA phosphorylates a protein known as Par-6, causing actication of aPKC and thus the phosphoylation of Lgl and its dissociation from the Par complex. When Lgl is no longer bound to the Par complex, a further protein, known as "Bazooka", may bind in its place. AurA activation thus effects a remodelling of the Par complex. As Knoblich further showed, the Par complex can only phosphorylate the Numb protein when Bazooka is present in the complex. Phosphorylated Numb is released from the cortex and because it diffuses only slowly through the cell it is restricted to a crescent on the opposite side.
Knoblich's results have identified a cascade of interactions among the various proteins required for restricting Numb's localization to a cortical crescent on the opposite side of the cell. A similar process was shown to operate in cultured human cells, so it is likely that the molecular mechanism responsible for regulating asymmetric cell division in Drosophila neuroblasts may control self-renewal and prevent tumour formation in other types of stem cell. The present findings are thus likely to have important ramifications in tumour biology. Indeed, mutations in the numb gene have been shown to cause uncontrolled growth of neuroblasts, leading to the formation of brain tumours and a similar phenotype results from expression of a constitutively active form of a PKC. Knoblich now reports that in this latter case the tumourigenic activity is completely removed by overexpressing Numb. The human Numb analogue is known to act as a suppressor of breast cancer, whereas the Lgl homologue has been implicated in metastasis of colon carcinomas (tumours are more aggressive in the absence of Lgl). The potential implications of Knoblich's latest results for human therapy are obvious, although Knoblich stresses that they lie well in the future.
Publication: Frederik Wirtz-Peitz, Takashi Nishimura, and Juergen A. Knoblich: Linking Cell Cycle to Asymmetric Division: Aurora A Phosphorylates the Par Complex to Regulate Numb Localization. Cell, October 3, 2008
F.W.P. was supported by a Ph.D. fellowship of the Boehringer Ingelheim Fonds; T.N. is supported by a long-term fellowship of the HFSP; work in J.A.K.'s lab is supported by the Austrian Academy of Sciences, FWF, WWTF, EU EUROSYSTEMS, and ONCASYM.Contact:
Dr. Heidemarie Hurtl | idw
What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering