Implicaciones funcionales de la fosforilación de stim1 mediada por erk1/2control de rutas de señalización y migración celular

Laburpena

STIM1 is an endoplasmic reticulum protein that serves as a Ca2+ sensor within the endoplasmic reticulum (ER). Under activation of Ca2+ release from the ER, STIM1 translocates to plasma membrane-ER junctions where it activates plasma membrane Ca2+ channels and the Ca2+ influx pathway termed store-operated Ca2+ entry (SOCE). To become fully activated STIM1 is phosphorylated at ERK1/2 target sites (Ser575, Ser608, and Ser621). This phosphorylation is related with STIM1 activation and is required for the dissociation from the end-binding protein 1 (EB1). Furthemore, IGF-1 triggers STIM1 phosphorylation in the aforementioned residues. IGF-1 activates also STIM1-EB1 dissociation and induces NFAT translocation, that is delayed with STIM1- 3A or STIM1-EB1 tandem protein over-expression, confirming that both STIM1 phosphorylation and STIM1-EB1 dissociation are required for fully STIM1 activation. SOCE regulates cell migration and STIM1 phosphorylation is related to this process. We show here that intracellular distribution of phospho-STIM1 is mainly localized in membrane ruffles and STIM1-3A delays cell migration, increases the number and size of focal adhesions and slows down membrane ruffling dynamics. These results suggest that Ca2+ entry through SOC channels regulates cortactin dynamics and that STIM1 phosphorylation at ERK1/2 target sites is necessary for this process.