Many proteins in our cells are decorated with sugar molecule add-ons, which are essential for the functions of these proteins. One particular type of sugar modification, called GlcNAc, is of key importance, because our cells cannot survive without it.
Researchers at the Max Planck Institute of Biochemistry in Martinsried near Munich have recently uncovered a previously unknown mechanism explaining how this sugar residue affects protein function and thereby influences our development. These results have been published in the journal Developmental Cell.
Proteins are responsible for all vital processes in the cells of our body. However, they are not alone: tiny sugar molecules are decorating many proteins and they often are important to make them work properly. One particular type of sugar modification, called O-linked N-acetylglucosamine - in short called O-GlcNAc - seems to be of fundamental importance, because our cells cannot survive without it.
Yet why exactly human cells die if their proteins lack the O-GlcNAc tag remains a mystery. Jürg Müller and Maria Cristina Gambetta at the Max Planck Institute of Biochemistry in Martinsried near Munich recently have addressed this question and set out to identify substrate proteins whose modification by O-GlcNAc is essential for biological processes. For their experiments the researchers made use of the less complex model organism Drosophila, also known as the fruit fly.
The researchers found that flies lacking O-GlcNAc show serious defects during their development: their cells fail to ‘remember’, which part of the body they were supposed to form. “Interestingly, we also observed the very same defects in flies lacking any member of the so-called Polycomb group of proteins” explains Maria Cristina Gambetta, the first author of the study.
The Polycomb proteins permit cells to remember their fate by specifically silencing genes, which are not needed in those cells. However, how did these two results fit together? Why are the consequences of missing O-GlcNAc so similar to the consequences of missing Polycomb proteins?
The researchers were able to show that the function of one specific Polycomb protein, called Polyhomeotic - in short Ph - only functions properly if it carries the O-GlcNAc tag. The researchers found that the O-GlcNAc tag is critical to prevent Ph from forming large macromolecular clumps, which would interfere with its ability to silence its target genes.
“This constitutes a previously unappreciated biochemical function of O-GlcNAc, namely to prevent the aggregation of a protein under normal physiological conditions”, explains Jürg Müller. “Moreover, we have been able to show that Polycomb repression is the most critical cellular process in flies that relies on O-GlcNAc.”
But how do these findings help us to advance our understanding of why our human cells need O-GlcNAc? In the latest study the researchers found out that fly and human Ph show high similarity. Consequently, also the human protein required O-GlcNAc in order to not clump together with other Ph proteins. “It will be interesting to further investigate, whether defective silencing of Polycomb target genes is also a major biological process that goes awry in human cells lacking O-GlcNAc”, Gambetta sets the agenda for the upcoming experiments. The results have recently been published in the journal Developmental Cell.
M.C. Gambetta and J. Müller: O-GlcNAcylation Prevents Aggregation of the Polycomb Group Repressor Polyhomeotic. Developmental Cell, November 26, 2014.
Dr. Jürg Müller
Laboratory of Chromatin Biology
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Phone: +49 (0) 89 8578-2824
http://www.biochem.mpg.de/4876634/058_mueller_glcnac - Link to the press release
http://www.biochem.mpg.de/mueller - Research group "Chromatin Biology"
http://www.biochem.mpg.de/news - More press releases of the MPI of Biochemistry
Anja Konschak | Max-Planck-Institut für Biochemie
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences