CONICET | Buscador de Institutos y Recursos Humanos

Folding intermediates and irreparable folding species are retained in the ER by the lectins calreticulin (CRT) and calnexin. Central to this process is the enzyme UDP-Glc:glycoprotein glucosyltransferase (GT), which regenerates the monoglucosylated glycan recognized by both lectins. In vitro experiments show that this enzyme recognizes exposed hydrophobic aminoacids, preferentially when they are forming patches in advanced folding intermediates. This property allows the participation of GT not only in the quality control of protein tertiary structure, but also in the supervision of oligomers assembling. Interestingly, the different components of the folding quality control system seem to work in coordination. For instance, recent evidence suggests that the long term activity of GT is strongly dependent on the presence of CRT, as this lectin prevents GT inhibition by monoglucosylated glycans. Finally, besides working as a lectin-chaperone, CRT is one of the main calcium buffers of the endoplasmic reticulum. Although it was originally described that the lectin activity of CRT depends on calcium, we found that both activities are mutually independent in vitro. Accordingly, ER calcium depletion in Trypanosoma cruzi did not affect the association of cruzipain with CRT.