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Switch protein also influences the cytoskeleton

21 May 2010 Ruhr-Universitaet-Bochum

The protein Ras is known as the switch for cell division when it is activated. Mutations in Ras and its interaction partners can thus lead to the development of cancer. Researchers in Bochum have now discovered another unexpected capability of Ras, namely that it, by interacting with another protein, controls the synthesis of the cytoskeleton responsible for the structure and stability of the cell. Prof. Christian Herrmann’s team managed to demonstrate Ras-controlled synthesis of the cytoskeleton in a test tube. The scientists have reported their findings in the current edition of the Journal of Biological Chemistry.

Ras mutations often lead to cancer

The Ras molecule is a member of a family of proteins that has a number of important cell functions. The molecules are either in an active or in an inactive state and are thus regarded as molecular switches. In the “on” state, Ras can interact with a further family of proteins, the so-called effectors, which in turn can result in the triggering of basic processes within the cell, such as cell division. Mutations in Ras and its effectors are a common reason for the development of cancer. The interest in research into this protein is thus commensurately high. By now scientists all over the world have highly detailed knowledge of its mode of action. 

Entirely new function of Ras identified

Biochemists from the Ruhr-University in Bochum have supplemented this data with a totally unexpected function. The research group under the auspices of Prof. Christian Herrmann (Faculty of Chemistry and Biochemistry) have published a report on the Ras effector NORE1A (Novel Ras Effector 1). The scientists were able to demonstrate that NORE1A, in contrast to the well-known effectors, is not required to control cell division, but involved in the synthesis of the cytoskeleton. The cytoskeleton, which is responsible for the structure and stability of the cell, is composed of the protein tubulin, amongst others. The tubulin molecules cluster as bases. They develop into nanotubes, i.e. microtubules, and give the cell an internal structure. The Ras effector NORE1A is involved at exactly this point, the so-called nucleation of tubulin. Prof. Herrmann pointed out that it is particularly surprising that this process can be directly regulated via the molecular switch Ras. The research group managed to simulate the reaction in a test tube. The addition of Ras impedes the synthesis of the cytoskeleton.

Experimentally difficult to access

The investigation of the NORE1A-induced tubulin nucleation was experimentally difficult to access. Prof. Hermann and his research group worked with experts from the National Institute for Medical Research in London and the University of Virginia. He emphasized, that this proof that Ras amazingly enough exerts a direct regulatory effect on the microtubule cytoskeleton, could never have been attained without this close international collaboration.

Attached files

  • It is also possible to demonstrate the dependence of the synthesis of microtubules on Ras within the cell. The microtubules in WI-38 cells, discernible as red filaments (A), were made visible by immunofluorescence microscopy. They are no longer visible (B) if activated Ras is artificially inserted into the cell. A similar effect is attained if one ensures that there is no NORE1A within the cell (C). This implies that NORE1A is necessary for the cells to be able to synthesize microtubules, whereas Ras can inhibit this process.

  • A) Proof of the NORE1A induced tubulin nucleation. This process is easy to observe in the photometer. The increase in the optical density (OD 350) of the sample solution clearly indicates the dependence of the tubulin nucleation on the concentration of the NORE1A added. B) The addition of the activated molecular switch Ras (Ras.GppNp) impedes the process of the NORE1A induced tubulin nucleation. The optical density decreases with increasing Ras concentration.

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