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Nerve cells must perform millions of neuronal processes and form connections between them during embryonic development to ensure that the nervous system will function properly. Dr. Marta Rosário and Prof. Walter Birchmeier from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch (Germany), a member of the Helmholtz-Association of National Research Centres, have discovered a novel regulator which is crucial for this process and which they named NOMA-GAP (Neurite-Outgrowth MultiAdaptor RhoGAP).They show that NOMA-GAP is essential for the function of the nerve growth factor (NGF), itself a crucial factor for the functioning of the nervous system and for nerve cell survival. NOMA-GAP connects NGF and its receptor to two signalling pathways which are critical for the outgrowth and extension of neuronal processes. Mutations in this protein network can result in neurodegenerative diseases such as Alzheimer`s Disease and may underlie the development of mental retardation in Downs syndrome. The researchers in Berlin believe that their findings will contribute to the understanding of the onset of such diseases. Their results are published in the Journal of Cell Biology (Vol. 178, No. 3, pp.503-516, 2007).
Dr. Marta Rosário, a Portuguese cell biologist from Walter Birchmeier´s laboratory, discovered the regulator in differentiating mouse nerve cells. She could show that NOMA-GAP is found in the neural tube, the earliest embryonic phase of the nervous system, and later in both the peripheral and central nervous system during development. Moreover, it is absolutely required for the formation of neuronal processes as stimulated by NGF.
What makes NOMA-GAP especially interesting for the cell biologists is the fact that is has two different functions. "On the one hand it is like an electrical socket, into which you can put several different plugs", Dr. Rosário explains. "That is why it belongs to the group of multiadaptor proteins." These proteins are capable of organizing large, temporary protein complexes necessary for protein-protein interactions and send their information to different signalling pathways in a very regulated manner.
In addition, NOMA-GAP is an enzyme, namely a RhoGAP, an important feature for building and re-structuring the cellular skeleton. As Dr. Rosário points out, "We have demonstrated, for the first time, that this single protein combines those two functions".
*The Neurite-Outgrowth MultiAdaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42
Marta Rosário1*, Renate Franke1, Christien Bednarski1 and Walter Birchmeier1
1 Max Delbrück Center for Molecular Medicine; Robert-Rössle-Strasse 10, 13092 Berlin, Germany
*Corresponding author: Tel: +49 30 9406 3791; Fax: +49 30 9406 2656
Email: m.rosario@mdc-berlin.de
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10
13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
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