Abstract
The goal of this thesis is to investigate the phenomena, the mechanism and the function of nuclear-localized membrane receptor, Ror1. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system development. Following transfection, the nuclear distribution patterns of transiently expressed cytoplasmic Ror1 were observed. Serial deletion constructs were then used to map the juxtamembrane domain of Ror1 (aa_471–513) for this nuclear translocation activity. Subsequent immunofluorescence analysis by cotransfection of Ran and Ror1 implied that the nuclear translocation event of Ror1 might be mediated through the Ran pathway. The two FKBP fusion Ror1 including membrane-localized (M-Ror1) and nuclear-localized (N-Ror1) Ror1 were stably expressed under doxycycline regulation in HeLa TF cells. The whole-genome microarray expression analysis of gene expression indicated activated M-Ror1 could affect genes involved in Wnt signaling pathway, and activated N-Ror1 could regulate actin cytoskeleton. The observation of phenotype also showed that activated N-Ror1 would result in the formation of F-actin stress fiber and the increased cell motility. This study might be beneficial in future research to understand the Ror1 biological signaling pathway.