CONICET | Buscador de Institutos y Recursos Humanos

Rab1b belongs to the Rab-GTPase family that regulates membrane trafficking and signaltransduction systems able to control diverse cellular activities, including gene expression.Rab1b is essential for endoplasmic reticulum?Golgi transport. Although it is ubiquitouslyexpressed, its mRNA levels vary among different tissues, but the importance of thisvariability in Rab expression levels remains unclear. In this study we examined differentcellular effects induced by changes in Rab1b levels.FRTL-5 thyroid cells were chosen as a secretory model. In these cells, secretory activity isinduced by thyroid stimulating hormone (TSH) which stimulates the synthesis of cellspecific proteins that require the secretory pathway to reach their final destination. Toassess the effects of Rab1b on the secretory response in our model, we performedtransient transfections with GFP-Rab1bwt or its dominant-negative mutant. In order toevaluate the consequences of Rab1b depletion, silencing of Rab1b was carried out in thesame cell line. Analysis were performed comparing cells grown in basal (-TSH) orstimulated (+TSH) condition.Our results show that TSH addition increases NIS (Sodium/Iodide Symporter), as well asRab1b and GM130. Moreover, an increase in Rab1b enhances NIS expression and NISpromoter activity, suggesting a role of Rab1b in NIS activation pathway. On the otherhand, we also found that Rab1b inhibition blocked the TSH-stimulated NIS and GM130increase.Our data strongly suggests that activation of secretion (or membrane transport) by asecretory stimulus induces an increase in Rab1b levels. Additionally, changes in Rab1bexpression in FRTL5 cells modify the specific TSH response. Our results show, for the firsttime, that changes in Rab1b levels modulate gene promoter activity and strongly suggestthat a Rab1b increase is required to elicit a secretory response.