Abstract for presentation at 11th International Congress of Human Genetics

Dynamic regulation of dyslexia candidate gene product DYX1C1 in cell stress reaction

  • Nina Kaminen-Ahola, Department of Medical Genetics, University of Helsinki, Finland
  • Dr Roberta Linkai, Department of Neurology, University of Helsinki, Hungary
  • MD, PhD Perttu Lindsberg, Department of Neurology, University of Helsinki, Finland
  • Prof Juha Kere, Department of Medical Genetics, University of Helsinki, Department of Biosciences and Nutrition, Karolinska Institutet, Hudding, Finland

    • The dyslexia candidate gene DYX1C1 encodes a 420 amino acid protein with three tetratricopeptide repeat (TPR) domains. In unchallenged transfected COS-1 cells and in a fraction of cortical neurons and white matter glial cells in post-mortem brain tissue samples it localizes mainly to the cell nucleus. Its function is still unclear, but examination of DYX1C1 expression in human ischemic brain tissue suggested that it is changed dynamically in the face of metabolic challenge. Both predictions and recent data indicate that DYX1C1 interacts with heat shock protein 70 (HSP70) and the CHIP protein (C-terminus of Hsp70-interacting protein; official nomenclature STUB1). The sequence of DYX1C1 contains a homology of the binding site of p23 which is a co-chaperone of HSP90. To investigate the role of DYX1C1 in stress reactions or metabolic challenge, we have done in vivo studies with permanent ischemia brain damage of rats and in vitro studies with heat shocked transient transfected cells. The co-localization and potential interactions were examined with HSP70, HSP90 and CHIP. DYX1C1 was mainly in the nucleus and CHIP in the cytoplasm after co-transfection, but immediately after heat shock, both proteins co-localized in the cytoplasm. Within 3 h of the heat shock, the co-localization had mostly cleared. Our data indicate rapid regulation of DYX1C1 protein translocation in the face of cellular challenge.

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