CONICET | Buscador de Institutos y Recursos Humanos

Posttranslational arginylation of proteins consists in the covalent union of an arginine into an acidic amino acid at the NH2-terminus by arginyl-tRNA protein transferase (ATE1). We demonstrated the arginylation of calreticulin (CRT) in vitro and in living cells. The arginylated form of CRT (R-CRT) was observed in the cytoplasm in contrast to the ER-CRT. It has been demonstrated that CRT affects cell adhesion by interaction with α-subunits of all integrin receptors. This interaction occurs via the highly conserved KxGFFKR sequence and is therefore hypothesized to play a crucial role in integrin function. In this work, by affinity chromatography in vitro, we show that when CRT is arginylated does not interact with integrins. Moreover, under stress conditions, R-CRT increased and cells had less adhesiveness to substrata compared to control cells. In addition, when ATE1-/- cells were transfected with full length CRT that overexpressed ER-CRT, attachment to substrate was improved. This results lead us to speculate that the increased levels of R-CRT is the responsible for impair adhesiveness. Thus, posttranslational arginylation of CRT seems to regulate its intracellular localization and cytoplasmic function. Supported by SECyT-UNC, CONICET, ANPCyT-PICT.