CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
STARD7 DEFICIENCY MODULATES CONNEXIN 43 EXPRESSION AFFECTING GOLGI APPARATUS AND CENTROSOME LOCATION DURING CELL MIGRATION
Autor/es:
ROJAS L; MIRANDA A.L.; FLORES-MARTIN J.; CRUZ DEL PUERTO M.M; KOURDOVA L.
Reunión:
Congreso; Reunión anual SAIC-SAFIS_SAI; 2018
Resumen:
StarD7 belongs to START domain protein family, which is involved in lipid transport, metabolism and signaling. Previous results from exploratory differential gene expression analysis in JEG-3 cells transfected with StarD7 siRNA demonstrated that connexin 43 (Cx43) mRNA is largely downregulated. In the present study we explored the effect of StarD7 siRNA on Cx43 expression and its association with Golgi apparatus and microtubule organization center (MTOC) location during polarized cell movement in the derived-first trimester trophoblast HTR8/SVneo cells. Additionally, the expression of several extracellular matrix (ECM) proteins was examined. Data from qRT-PCR and western analysis demonstrated a decrease in Cx43 mRNA and protein levels in cells transfected with StarD7 siRNA compared to control siRNA. A significant increase in the mRNA and protein levels of integrin α5, the mature integrin β1, β-catenin and nidogen-1 in silenced cells was determined. Also, StarD7 silencing lead to an increase in the amount of MMP9 secreted to the culture medium. Exogenous StarD7 expression was able to restore Cx43 and nidogen-1 expression in StarD7 silenced cells. Wound healing and transwell assays demonstrated that cell migration was decreased in StarD7 knockdown cells. Finally, StarD7 suppression lead to a disruption in Golgi apparatus organization and also to a lack in the ability of the cell to reorient MTOC/Golgi in a polarized migration.Collectively, our studies reveal that StarD7 deficiency leads to a diminution in Cx43 expression with a reprograming of genes encoding ECM or ECM associated proteins; and this outcome is linked to Golgi apparatus disruption and a deficiency to appropriately locate MTOC/Golgi during cell migration. All of these findings cause cell polarity defects and a decreased cellular migration. Supported by FONCyT, CONICET, SECyT-UNC.