Cells control the adhesion protein desmoplakin by modifying the tail end of the protein, and this process goes awry in some patients with arrhythmogenic cardiomyopathy, according to a study in The Journal of Cell Biology.
Desmoplakin is a key component of the adhesive junctions, known as desmosomes, that link cells together in tissues that undergo severe strain, such as the heart and skin. Its role is to anchor parts of the cytoskeleton to sites of cell-to-cell contact.
Kathleen Green and colleagues at Northwestern University Feinberg School of Medicine determined how modifying desmoplakin’s intracellular tail with phosphate and methyl groups affects the protein’s interaction with the cytoskeleton.
The enzyme GSK3 added phosphate groups to desmoplakin’s tail, and its loss spurred the protein to shift from desmosomes to the intermediate filaments. Blocking GSK3 slowed desmoplakin’s relocation from the intermediate filaments to the cells’ boundaries during desmosome formation.
Methylation of four arginine residues in desmoplakin’s tail had similar effects as phosphorylation. The team also found that methylation of one particular arginine, R2834, which is mutated in some patients with arrhythmogenic cardiomyopathy, was necessary for the phosphorylation of most tail serine residues because this modification drew GSK3 to desmoplakin. Mutating this arginine delayed desmoplakin’s assembly into desmosomes, weakening intercellular connections so that cell layers broke apart under mechanical stress.
The results show that phosphorylation and methylation make desmoplakin more dynamic. Cells might be able to fine-tune desmoplakin’s characteristics by adding and removing phosphates and methyl groups, and defects in this regulatory process might contribute to skin and heart diseases.
Albrecht, L.V., et al. 2015. J. Cell Biol. doi:10.1083/jcb.201406020
About The Journal of Cell Biology
The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works, and third parties may reuse the content for non-commercial purposes under a creative commons license.
For more information, please visit www.jcb.org .
Rita Sullivan King
Rita Sullivan King | newswise
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy