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

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

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 participates in the degradation of estrogen receptors alpha (ERα) and beta (ERβ), we hypothesized that the effects of DYX1C1 might be at least in part mediated through the regulation of ERs. 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.

Original languageEnglish (US)
Pages (from-to)2802-2812
Number of pages11
JournalHuman Molecular Genetics
Volume18
Issue number15
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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