ARGINYLATED CALRETICULIN: A PRO-APOPTOTIC PROTEIN?

LÓPEZ SAMBROOKS, CECILIA; CARPIO, MARCOS; HALLAK, MARTA

Florencia

Congreso; 8th IBRO WORLD CONGRESS OF NEUROSCIENCE.; 2011

Posttranslational arginylation of proteins consists in the covalent union of arginine in an acidic amino acid at the N-terminus position, which is mediated by arginyl-tRNA protein transferase (Ate 1). Although arginylation was discovered more than 40 years ago, the identity of proteins arginylated in vivo and its biological functions are largely unknown. We have characterized calreticulin (CRT) as substratum of this modification. This modified protein showed, in neurons and fibroblasts, a sub cellular localization different from that described for CRT within the endoplasmic reticulum. The arginylated form of CRT (R-CRT) was present in the cytosol and at the cell surface. We have determined that the cellular alteration of calcium homeostasis causing decreased cytosolic calcium level increased cytosolic R-CRT and promotes under different stress conditions the selective association of this protein to stress granules (SGs). SGs are formed in neurons and myelinizating cells in response to several stress stimuli similar to those that occur in neurodegenerative diseases and they contain pro-apoptotic factors. If the stress is not reversed the cells activates mechanisms of apoptosis. Under these conditions we also have observed that R-CRT is incorporated in the cell membrane. Moreover, we have showed that cells lacking the Ate 1 enzyme were significantly resistant to apoptosis compared to wild type cells. Thus posttranslational arginylation of CRT seems to regulate its intracellular localization, cell function and survival.