Regulation of Notch receptor signalling:

The control of cell differentiation during development requires communication between cells via diffusible growth factors and cell-cell adhesion mediated signalling molecules. The Notch receptor is an example of the latter class and regulates the timing and outcome of cell differentiation decisions in many different tissues during development.The Notch signal must be precisely regulated to prevent inappropriate signalling since misactivation of Notch can cause tumours.

Notch was first identified in Drosophila but has subsequently been identified in a range of vertebrate species, including four versions of the gene in humans.

The activity of Notch in vivo is precisely controlled spatially and temporally. Using the Drosophila model system, our group has identified a negative regulator of Notch called Suppressor of Deltex (Su(dx)), which belongs to an E3 class of ubiquitin ligase molecules that regulate endocytosis and proteolytic degradation of target molecules.

We have found that Su(dx) interacts with Notch at the cell surface and determines the subsequent sorting of Notch within the early endosome to enable its transfer to the late endosome. Furthermore we have found that endosomal sorting of Notch distinguishes between alternative mechanisms of Notch signalling.

External Contributions:

Editorial scientific advisory board of Molecular Membrane Biology.