Browsing Department of Cellular Biology and Anatomy Theses and Dissertations by Authors
DETERMINING THE MECHANISM OF EGALITARIAN-MEDIATED MRNA TRANSPORT IN DROSOPHILAGoldman, Chandler; Biomedical SciencesThe establishment of cell polarity is critical for performing complex functions including division and migration. As such, the loss of polarity is implicated in many diseases including cancers. To establish polarity, many cell types rely on the asymmetric sorting of messenger RNAs or mRNAs. These mRNAs are held in a translationally-repressed state until reaching their destinations. Upon arrival, translation is allowed to commence, giving rise to spatially restricted proteins. Often, mRNAs are transported to their destinations along microtubules via linkage to one of the sub families of microtubule motors, Dynein or Kinesins. The mechanism by which mRNAs are linked to these motors is unknown for the vast majority of localizing mRNAs. Drosophila oocytes and embryos display a great number of mRNAs that are localized to specific regions. The protein Egalitarian (Egl) has been shown to directly bind several mRNAs and participates in their microtubule-based transport by promoting linkage to cytoplasmic Dynein. In Aim 1 of this thesis, we aim to determine the mechanism by which Egl and its interacting partners, Dynein light chain (Dlc/LC8), and Bicaudal D (BicD), tether mRNAs to the Dyenin motor for transport. Dlc is required for Egl homodimerization, which promotes binding to mRNAs. BicD then preferentially associates with mRNA-bound Egl and links the complex to the Dynein motor. In Aim 2, we further investigate Egl’s role in mRNA transport by determining the critical amino acid residues within its RNA binding domain required for mRNA association.