UPS - Unconventional Protein Secretion

• Applicant: Professor Dr. Walter Nickel
• Subject Area: Cell Biology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 128127591

Two types of non-classical protein transport to the cell surface of eukaryotic cells have been described, processes that collectively have been termed 'Unconventional Protein Secretion' (UPS). The first type is represented by integral membrane proteins that can reach the cell surface in a Golgi-independent manner. The second type is being used by soluble secretory proteins that exit cells without any involvement of the endoplasmic reticulum (ER) and the Golgi system. While integrins are an example for membrane proteins transported by unconventional means, the class of soluble unconventional secretory proteins includes interleukin (IL) family members, fibroblast growth factors (FGF), macrophage migration inhibitory factor (MIF), galectins and acyl-CoA binding protein, macromolecules that are secreted from cells to regulate the immune response, cell growth and differentiation as well as angiogenesis. These are clearly very important proteins and an understanding of their mechanism of secretion is therefore of fundamental importance. We propose a network of leading European laboratories that will collaborate to elucidate these “unconventional pathways of protein secretion” at the molecular level. We will use advanced techniques such as iTRAQ and SILAC proteomics as well as genome-wide screening using RNA interference to identify essential components and to reveal the mechanisms regulating unconventional protein secretion.

• DFG Programme: Research Grants