Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

It takes a sugar to catch a sugar

05.12.2011
A single sugar molecule plays an outsized role in helping a glucose-transporting protein respond promptly to insulin signals

After every meal, the hormone insulin is released into the bloodstream, issuing instructions to target cells to begin taking up excess sugar. In some situations, however, cells stop responding to these signals; and this insulin-resistant state is associated with onset of type 2 diabetes. Unexpected findings from Tadashi Suzuki’s group at the RIKEN Advanced Science Institute in Wako have now revealed how a cellular malfunction may contribute to this insulin resistance1.


Figure 1: GLUT4 is normally retained within storage vesicles in the cytoplasm (top left), but is redistributed to the cell membrane within 30 minutes of insulin treatment (top right). However, the non-glycosylated N57Q mutant (bottom left) fails to respond to insulin and remains within cytoplasmic vesicles even after 30 minutes (bottom right) (scale bars, 10 ìm).
Copyright : 2011 American Society for Biochemistry and Molecular Biology

Suzuki and postdoctoral fellow Yoshimi Haga had originally sought to develop imaging strategies to track localization of proteins modified with carbohydrate groups in a process known as glycosylation. They tested their method with the glucose-transporter protein GLUT4 and developed a mutant version of the protein that lacks a glycosylation site, but the results led their study in a new direction. “We accidentally found that behavior of our N57Q mutant and the wild-type protein was quite different,” says Suzuki. “It was a completely serendipitous finding.”

Insulin-responsive cells typically maintain reservoirs of GLUT4 in bubble-like vesicles within the cytoplasm; insulin signals induce the transport of GLUT 4 to the cell surface, where it begins pumping glucose into the cell. The N57Q mutant, on the other hand, was largely unresponsive to insulin (Fig. 1). Suzuki and colleagues determined that, instead of gathering within storage vesicles, this protein tended to accumulate either at the cell surface or within ‘recycling vesicles’ that continually shuttle to and away from the plasma membrane.

The N57Q mutant retains normal glucose-transporting capabilities, suggesting that this modification acts primarily as a trafficking signal rather than influencing protein function. Accordingly, the researchers observed the same insulin-insensitive behavior when they used a chemical treatment to alter the glycosylation of normal GLUT4. “These results clearly suggest that there must be a mechanism that detects subtle differences in glycan structure on this protein to sort it into specific GLUT4 vesicles,” says Suzuki.

Several studies have found evidence that GLUT4 may be subject to altered glycosylation in a subset of patients with type 2 diabetes; and, these new findings provide a potential explanation for how malfunctions in this protein modification process could contribute to pathology. As a next step, Suzuki hopes to uncover more details about how this transport pathway intersects with the insulin response. “We believe that glycan-recognition molecules known as lectins should be involved in this process,” he says, “and we will try to identify these lectins and other players involved in the fine-tuning of intracellular trafficking of GLUT4.”

The corresponding author for this highlight is based at the Glycometabolome Team, RIKEN Advanced Science Institute

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

Further reports about: Advanced Investigator Grant GLUT4 N57Q RIKEN Science TV Suzuki cell surface type 2 diabetes

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 >>>