PhD Thesis Topic
Physiological implications of post-translational arginylation of proteins
The post-translational modifications (PTMs) of proteins broadly affect the biochemical properties of distinct substrates, modulating the structure, interacting capacity and subcellular localization of proteins and polypeptides. Arginylation is a PTM mediated by arginyl-tRNA-protein transferase (ATE1), which transfers Arg from arginyl-tRNA onto proteins that have an acidic amino acid or Cys as the N-terminal residue. The characterization of different in vivo arginylated proteins has allowed to ascertain how this PTM plays key roles in a variety of physiological processes including cell adhesion, apoptosis, and cellular stress response. We have previously demonstrated that calreticulin (CRT), an endoplasmic reticulum (IS) resident protein, is one of the arginylated substrates. We showed that a pool of CRT undergoes retro-translocation from the ER to the cytosol under conditions that reduce cytoplasmic Ca2+ levels. Moreover, we found that arginylated CRT (R-CRT) is essential for its association with stress granules (SGs) and promotes homodimers formation. As well, the apoptosis induction is associated with an increased R-CRT level at the cell surface. Considering the different locations, environments and conditions observed for R-CRT within the cell, our studies are aimed to uncover the functional implications that post-translational arginylation confers to CRT.