Abstract
BackgroundRasGrf1 is a guanine‐nucleotide releasing factor that enhances Ras activity. Human PTTG1 is an oncoprotein found in pituitary tumors and later identified as securin, a protein isolated from yeast with a reported role in chromosome separation. It has been suggested that RasGrf1 is an important upstream component of signal transduction pathways regulating Pttg1 expression and controlling beta cell development and their physiological response. At memory formation level, there are contradictory data regarding the role of RasGrf1, while Pttg1 has not been previously studied. Both proteins are expressed in the mammalian hippocampus, which is one of the key brain areas for spatial learning and memory.ObjectiveThe aim of this work was to study a potential link between RasGrf1 and Pttg1 in memory formation.MethodSpatial learning and memory test in the Pttg1 KO, RasGrf1 KO, and Pttg1‐RasGrf1 double KO and their correspondent WT mice using a Barnes maze.ResultsIn comparison with the WT control mice, Pttg1 KO mice learned how to solve the task in a less efficient way, suggesting problems in memory consolidation. RasGrf1 KO mice performance was similar to controls, and they learned to use the best searching strategy. Double KO mice reached a better spatial learning level than WT.ConclusionA role for Pttg1 in memory consolidation/formation is suggested, while our RasGrf1 KO mice do not show hippocampus associated memory defects.
Highlights
Scientific works have revealed that Ras-GRF proteins are important components of signaling pathways that mediate a variety of central nervous system functions, including hormonal production controlling body size, regulation of synaptic plasticity, and generation of specific forms of learning and memory (Feig, 2011)
Our laboratory showed that pancreatic islets of RasgGrf1 knock out (KO) mice display a specific transcriptional profile involving significantly reduced expression levels of Pttg1 that are probably linked to a regulatory role of RasGrf1 over the Pttg1 promoter
We have observed a dominance of Pttg1 over RasGrf1 with regard to the generation of these mouse pancreatic phenotypes, suggesting that RasGrf1 is an important upstream component of signal transduction pathways regulating Pttg1 expression and controlling beta cell development and physiological responses (Manyes et al, 2014)
Summary
Scientific works have revealed that Ras-GRF proteins are important components of signaling pathways that mediate a variety of central nervous system functions, including hormonal production controlling body size, regulation of synaptic plasticity, and generation of specific forms of learning and memory (Feig, 2011). Pttg is expressed in the mouse brain, especially in hippocampus and cerebellum (Lein et al, 2007) This observation, added to the fact that Pttg expression is impaired in the hippocampus of RasGrf KO mice, prompted us to analyze a potential mechanistic connection between these two proteins in memory formation processes. For this purpose, we tested in this report the spatial learning and memory of Pttg, Pttg1-RasGrf, and RasGrf null mice using a Barnes circular maze. It has been posited that the Barnes maze is less stressful to mice than water mazes (Rosenfeld & Ferguson, 2014)
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