Eleven million Euros are provided under this program to the project "Endotrack" (Tracking the endocytic routes of polypeptide growth factor receptor complexes and their modulatory role on signalling). "Endotrack" brings together an international team of 12 academic groups and SMEs (small and medium enterprises) from 7 different countries under the leadership of Prof. Marino Zerial from the Max Planck Institute of Molecular Cell Biology and Genetics.
The team of "Endotrack" aims at disclosing the thus far largely unexplored connection between endocytosis and the signalling of growth factors into the cells and understanding the complex regulation of these mechanisms. The knowledge gained as a result will help in the development of a new generation of tools to cure diseases like cancer and will contribute to explaining human congenital diseases which are associated with deregulation of growth factor signalling.
Processes such as absorption of macromolecules and fluids, the ingestion by cells in order to keep up their metabolism or the elimination of pathogens occurs via a cellular mechanism, called endocytosis (a process in which substances gain entry into cells without passing through the cell membrane). During endocytosis the cell takes in molecules (cargo) binding to components of the outer membrane of the cell: the cell membrane invaginates, enclosing the cargo and forming an intracellular vesicle. Thousands of vesicles transport their cargo through the cell every minute via a complex network of cellular pathways. Depending on its fate, the internalised cargo is either recycled and transported back to the cell surface via the recycling pathway, or is digested by being delivered to the degradative pathway.
In the past few years, it has become apparent that endocytosis not only plays a role in the uptake of nutrients but is also an important tool for transmitting signals from the outside to the inside of the cell. Molecules such as growth factors bind to, and activate, specific receptors on the membrane. The receptor passes the activation signal onto other cellular molecules that transmit it further. The domino effect of this activation cascade propagates and amplifies the signal throughout the cell thereby affecting activation of numerous cellular components. Eventually, the signal reaches the nucleus where it regulates gene expression.
Overall, signalling from growth factors is a highly specific and fine-tuned process. Up until now little has been known on how growth factor signalling is regulated through endocytic pathways, which regulators are involved, how the signal is passed on under different conditions and how the pathways differ from various growth factors.
Endotrack now aims at understanding how signalling from growth factors is regulated by the endocytic pathways and how modulation of these routes affects signalling. The identification of regulators of the different endocytic pathways is important for this process and therefore intracellular endocytic routes of different classes of growth factor complexes will be examined and the specific regulators defined. Endotrack will shed light on growth factor signalling not only in cell culture but also in animal disease model systems to get a clearer picture on how growth factor signalling causes diseases.
Endotrack has started on February 1, 2006 and will continue for four years.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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