Rer1: A new Notch in apical sorting and vesicular trafficking.

Retrieval-to-ER 1 (Rer1) acts in protein quality control, ensuring proper protein structure and assembly of multisubunit complexes. We have earlier shown that Rer1 regulates the assembly of gamma-secretase complex, a protease cleaving amyloid precursor protein (APP) and Notch, and a known risk factor for Alzheimers disease. In addition, we have demonstrated that Rer1 directs the organisation and function of cilia, as well as other apically-located cellular domains. In order to genetically dissect this role, and further investigate its other functions in vivo, we have initiated the characterization of rer1 in the fruit fly (Drosophila). Preliminary results indicate that Rer1, by regulating apical sorting and vesicular trafficking, affects the formation of eyes and bristles (external sensory organs of the fly), as well as their patterning. Novel data also suggests that Rer1 is an important regulator of Notch and planar cell polarity signaling. Here we propose several strategies to further dissect these roles making use of a genetically tractable model organism and a set of tools that are already developed, and postulate that investigation of Rer1s physiological functions will reveal novel aspects of regulation of signalling pathways important for human health and disease.

Keywords:Drosophila, Rer1, Trafficking, Notch, PCP

Disciplines:Systems biology