STARD7 DEFICIENCY MODULATES CONNEXIN 43 EXPRESSION AFFECTING GOLGI APPARATUS AND CENTROSOME LOCATION DURING CELL MIGRATION

Mar del Plata

Congreso; SAIC-SAI-SAFIS 2018; 2018

SAIC

StarD7 belongs to START domain protein family, which is involved inlipid transport, metabolism and signaling. Previous results from exploratorydifferential gene expression analysis in JEG-3 cells transfectedwith StarD7 siRNA demonstrated that connexin 43 (Cx43)mRNA is largely downregulated. In the present study we exploredthe effect of StarD7 siRNA on Cx43 expression and its associationwith Golgi apparatus and microtubules organization center (MTOC)location during polarized cell movement in the derived-first trimestertrophoblast HTR-8/SVneo cells. Additionally, the expression ofseveral extracellular matrix (ECM) proteins was examined. Datafrom qPCR and western analysis demonstrated a decrease in Cx43mRNA and protein levels in cells transfected with StarD7 siRNAcompared to control siRNA. A significant increase in the mRNA andprotein levels of integrin α5, the mature integrin β1, β-catenin andnidogen-1 in silenced cells was determined. Also, StarD7 silencinglead to an increase in the amount of MMP9 secreted to the culturemedium. Exogenous StarD7 expression was able to restoreCx43 and nidogen-1 expression in StarD7 silenced cells. Woundhealing and transwell assays demonstrated that cell migration wasdecreased in StarD7 knockdown cells. Finally, StarD7 suppressionlead to a disruption in Golgi apparatus organization and also to alack in the ability of the cell to reorient MTOC/Golgi in a polarizedmigration.Collectively, our studies reveal that StarD7 deficiency leads to adiminution in Cx43 expression with a reprograming of genes encodingECM or ECM associated proteins; and this outcome is linked toGolgi apparatus disruption and a deficiency to appropriately locateMTOC/Golgi during cell migration. All of these findings cause cellpolarity defects and a decreased cellular migration.