Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia

Satu Massinen, Kristiina Tammimies, Isabel Tapia-Páez, Hans Matsson, Marie-Estelle Hokkanen, Ola Söderberg, Ulf Landegren, Eero Castrén, Jan-Åke Gustafsson, Eckardt Treuter, Juha Kere
2009 Human Molecular Genetics  
Dyslexia, or specific reading disability, is the unexpected failure in learning to read and write when intelligence and senses are normal. One of the susceptibility genes, DYX1C1, has been implicated in neuronal migration, but little is known about its interactions and functions. As DYX1C1 was suggested to interact with the U-box protein CHIP (Carboxy terminus of Hsc70-Interacting Protein), which also participate in the degradation of estrogen receptors alpha (ERα) and beta (ERβ), we
more » ... d that the effects of DYX1C1 might be at least in part mediated through regulation of estrogen receptors. ERs have shown to be important in brain development and cognitive functions. Indeed, we show that DYX1C1 interacts with both ERs in the presence of 17β-estradiol, as determined by co-localization, co-immunoprecipitation and proximity ligation assays. Protein levels of endogenous ERα or exogenous ERβ were reduced upon over-expression of DYX1C1, resulting in decreased transcriptional responses to 17β-estradiol. Furthermore, we detected in vivo complexes of DYX1C1 with ERα or ERβ at endogenous levels along neurites of primary rat hippocampal neurons. Taken together, our data suggest that DYX1C1 is involved in the regulation of ERα and ERβ, and may thus affect the brain development and regulate cognitive functions. These findings provide novel insights into the function of DYX1C1 and link neuronal migration and developmental dyslexia to the estrogen signaling effects in the brain. by guest on November 7, 2016 http://hmg.oxfordjournals.org/ Downloaded from neuronal migration and neuronal survival in the developing cortex and Erβ knock-out (KO) mice present very similar phenotypes as the post-mortem brains of dyslexic individual (9, 11). by guest on November 7, 2016 http://hmg.oxfordjournals.org/ Downloaded from by guest on November 7, 2016 http://hmg.oxfordjournals.org/ Downloaded from by guest on November 7, 2016 http://hmg.oxfordjournals.org/ Downloaded from
doi:10.1093/hmg/ddp215 pmid:19423554 fatcat:44543htdrrc6bbv2zoeb7w2zwy