Regulation of Dab1 Splicing and Phosphorylation in Developing Neuronal Cells

• Author / Creator

  Dutta,Indrani

• The Reelin signaling pathway is involved in the migration of neurons during brain development. Reelin binding to the receptors VLDLR (Very Low Density Lipoprotein Receptor) and ApoER2 (Apolipoprotein E Receptor 2) leads to Dab1 phosphorylation, thereby activating a cascade of downstream pathways.
  Here, we show that the neuronal splicing factor Nova1 is involved in the exclusion of Dab1 exons 9b and 9c. In particular, the expression of Nova1 isoform 2 (without its penultimate exon 4), coincides with exclusion of Dab1 exons 9b and 9c in a neuronal P19 cells. Nova1 knockdown in P19 cells results in increased inclusion of Dab1 exons 9b and 9c.
  We also show that Dab1 phosphorylation is regulated by the Shp-2 phosphatase. Intriguingly, in addition to its role as a phosphatase, Shp-2 can function as an adapter protein to recruit kinases that phosphorylate Dab1 in P19 cells but not HEK293T cells. These results suggest an additional level of complexity to the regulation of Dab1 phosphorylation during neuronal development.

• Subjects / Keywords

  • Nova1
  • Splicing
  • Shp-2
  • Dab1

• Graduation date

  Spring 2014

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3XG9FK4D

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.