Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Conserved kinase protects cells from endosomal traffic jam

09.03.2011
Some molecules have a single, highly specific function in physiology, while others have a much broader remit. Kinases in the IKK family are of the latter sort, playing a variety of roles. A new report from RIKEN shows that this factor regulates shuttling of endosomes in the tips of growing mechanosensory bristles.

Some molecules have a single, highly specific function in physiology, while others have a much broader remit. Kinases in the IKK (inhibitor of nuclear factor êB (NF-êB) kinase) family are of the latter sort, playing a variety of roles in the immune system, cancer, and differentiation. Previous work with a related kinase, IKKå, in Drosophila has shown that this protein regulates the cytoskeleton and cell elongation in a number of contexts. It has yet to be shown, however, how it accomplishes this.


Activated IKKå (Magenta) accumulates at the tips of growing bristles, and actin bundles (green) run along the long axis of growing bristles.

A new report by Tetsuhisa Otani in the Laboratory of Morphogenetic Signaling (Shigeo Hayashi, Group Director) and colleagues, working in collaboration with the CDB Electron Microscope and Proteomics labs, does just that. In an article published in Developmental Cell, the groups show that this factor regulates shuttling of endosomes in the tips of growing mechanosensory bristles, converting the direction of their trafficking from incoming to outward bound.

Bristles form from single cells during the fly’s pupal stage. A previous report had indicated that IKKå is expressed at the tips of these structures. Otani looked at the active, phosphorylated form of the molecule and found that it indeed accumulated at the tips of growing bristles. He looked closer at cytoskeletal organization in these structures in wildtype and IKKå mutants, and found that in the mutant bristles, actin bundles were poorly organized and frequently had failed to attach to their anchor points in the cell cortex. Transmission electron microscopy further showed that while microtubules in mutants maintained their usual orientation with the respect to the bristle, an abnormal number of vesicles had accumulated in this space, suggesting that vesicle transport was somehow affected.

An examination of vesicle markers turned up a promising candidate in Rab11, a recycling endosome protein known to be essential in bristle morphogenesis. In contrast to its tendency to cluster around the tip in control animals, Rab11 was clumped in the bristle shaft in IKKå mutants. Other endosome markers also showed aberrant localization. The effect was replicated in cultured cells, in which mutant IKKå caused Rab11 to aggregate.

What then was the link between the defects in actin bundles and endosome distribution in IKKå mutants? Looking at the timing of these events, Otani found that Rab11 accumulation precedes the misrouting of actin, and was unaffected by various mutations that disturb the bundling of actin filaments, suggesting that IKKå’s roles in Rab11 distribution and actin bundling are independent.

He next used photobleaching and time-lapse imaging to track the localization of Rab11 over time. Rab11 normally moves along the bristle, shuttling between shaft and tip in a state of dynamic equilibrium. This rate and overall directionality of this back-and-forth varied, and was at its highest during bristle elongation. Looking for a mechanism, the group examined functional relationships between IKKå, Rab11, and the Rab11 effector, Nuf, which binds to Rab11 and the Dynein light intermediate chain (a component in microtubule trafficking). What they found pointed to opposing roles for IKKå and Nuf in the trafficking of Rab11. This antagonistic effect appears to be due to the phosphorylation of Nuf at a specific amino acid (serine 225) by IKKå. Preliminary experiments using IKKå homologs in mammalian cells suggested that the function of this factor in the trafficking of recycling endosomes is conserved.

"In addition to their role as vehicles for cellular materials, endosomes also serve as a platform for various signaling activities in cell proliferation and immunity,” says Hayashi. “The identification of new downstream targets of IKKå sheds light on the roles of endosomal trafficking in morphogenesis, innate immunity, and cancer."

[ Contact ]
Douglas Sipp : sipp(at)cdb.riken.jp
TEL : +81-78-306-3043
RIKEN CDB, Office for Science Communications and International Affairs
Journal information
Dev Cell. 2011 Feb 15;20(2):219-32.
'IKKɛ Regulates Cell Elongation through Recycling Endosome Shuttling.'
Otani T, Oshima K, Onishi S, Takeda M, Shinmyozu K, Yonemura S, Hayashi S.

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>