Changes in CREB3L2 transcription factor in cell differentiation models

Buenos Aires

Congreso; Reunión conjunta de sociedades de biociencias; 2017

CREB3L2 is a member of the CREB3 family of bZip transcription factors that show tissue-specific expression patterns. Although they have been described to participate in cell differentiation in various tissues by regulating the secretory machinery, very little is known about their role in the nervous system. Our goal is to analyze the regulation of the secretory pathway and the participation of CREB3L2 in cell development and differentiation models, specifically in neuronal cells. We are working on two models: one of them are PC12 cells, which can differentiate to neuron-like cells upon treatment with NGF, and the other one are hippocampal cells in culture obtained from rat embryos. We found that NGF increases significantly mRNA and protein levels of CREB3L2, while the other members of the CREB3 family do not respond the same way. Moreover, we show that NGF induces a time-dependent increase in protein levels of different markers of the early secretory pathway. The NGF-induced effect on CREB3L2 is abolished when cells are incubated with U0126 and H89, pharmacological inhibitors of MEK1 and MEK2 MAPK kinases and PKA, respectively. We also have evidence that, in hippocampal neurons in culture, there is a time-dependent increase in protein levels of CREB3L2 and secretory pathway factors as well. Our data suggest that: a) differentiation process goes along with an increase in proteins of the early secretory pathway; b) only CREB3L2 but not the other CREB3 transcription factors accompanies this process; and c) increase in CREB3L2 is both ERK and PKA dependent, proposing a dual regulation of this transcription factor. Further analyses are needed to investigate the molecular mechanisms underlying these changes and to elucidate the specific function of CREB3L2 in both models.