Sugar molecules are crucial to cell adhesion, the specific interaction between cells, and hence to the development of the embryo. This is the conclusion reached by Prof. Dr. Sabine Strahl and her team at the Centre for Organismal Studies at Heidelberg University. Their research shows that a special form of glycosylation, in which sugar molecules bind to proteins, is essential to the function of E-cadherin-mediated cell adhesion. According to Prof. Strahl, differentiation of the embryo is impossible if this protein modification is lacking. The results of the research were published in the journal PNAS.
In the early phase of embryonic development, the fertilised egg divides, forming a ball of loosely bound cells called the morula. For a compact cell packet and finally a complex organism to develop, the cells first need to bind tightly together. Cell adhesion molecules like E-cadherin are essential in this process. Cadherins are proteins that enable tissues to bind together and cells to communicate with one another. In all living organisms, numerous sugar molecules are bound to proteins after biosynthesis. This process, called glycosylation, is critical for growth and development. "The lack of certain sugar residues can lead to serious congenital development disorders in humans," explains Prof. Strahl.
The research team was now able to demonstrate in the mouse model why a certain type of glycosylation, called protein O-mannosylation, is critical to early embryonic development. The researchers proved that the E-cadherin protein carries mannose, sugar molecules present on the surface of the embryonic cells as of the four-cell stage of development. If biosynthesis of these E-cadherin-bound sugar residues is inhibited, functional cell connections cannot form and the cells cannot bind together with any stability. This leads to death of the embryo even before it can embed itself in the womb.
"The causal relationship we demonstrated between the sugar residues and cadherin-mediated cell adhesion shows that this protein modification is much more important than originally believed," says Sabine Strahl. "In view of the important functions of cadherins in development processes in vertebrates as well as in tumour metastasis, our work is extremely relevant in many areas of the life sciences and medical research." Based on the results of their research, the Heidelberg scientists now plan to investigate the significance of this protein modification in the genesis of cancer.
- M. Lommel, P. R. Winterhalter, T. Willer, M. Dahlhoff, M. R. Schneider, M. F. Bartels, I. Renner-Muller, T. Ruppert, E. Wolf, S. Strahl. Protein O-mannosylation is crucial for E-cadherin-mediated cell adhesion. Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1316753110
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