[RESUMEN] ABSTRACT

Different cellular proteins have to be sorted and transported to specific places within the cell, where they will perform their function. In the case of membrane proteins, once they are synthesized by the ribosomes, they are translocated to the Endoplasmic Reticulum (ER) due to the presence of signal peptide sequences that address them to this location. In the ER, they suffer modifications such as glycosilation and proteolysis, and then, they are transported to the Golgi Apparatus (GA) where they undergo new modifications and finally are sorted to their final destination, which can be extracellular secretion or plasma membrane insertion. We have studied this process for the Transforming Growth Factor-alpha (TGF-alpha), a transmembrane cell surface molecule. We have found that a signal, necessary for its correct trafficking is located in the last amino-acid, which is a valine. A mutation in this residue causes retention in the ER, stopping the transport process. Investigating the transport machinery involved in this signal, we have found a molecule located in the ER and that establishes a stable interaction with wild type TGF-alpha but not with the mutant form where valine C-terminal is substituted. This protein is called TACIP18 and is probably the first member of a molecular pathway involved in the transport of proteins with similar intracellular motifs.