Determining the role of Apc2 and interacting proteins in dendrite organization of Drosophila neurons.

Open Access
Guignet, Michelle Ann
Area of Honors:
Biochemistry and Molecular Biology
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Melissa Rolls, Thesis Supervisor
  • Joseph C. Reese, Honors Advisor
  • APC2
  • microtubule polarity
  • branch point localization
Microtubules are extremely important in defining cell shape and structure, but also provide polarized tracks in the cell to assist in long-range transport in neurons. Understanding the cellular processes controlling this polarity may give insight into understanding various neurological diseases. It has been shown that adenomatous polyposis coli protein 2 (APC2), a plus end binding protein, plays a role in maintaining the polarity of these microtubules in dendrites of neurons. More importantly, a recent study has shown that APC2 is specifically localized to dendrite branch points to maintain polarity at these sharp junctions. Understanding what controls the localization of APC2 to these distinct locations within the cell is crucial to understanding how the organization of these microtubules is maintained. Using RNA interference to knock down the expression of different interacting partners of APC2, we determined that microtubule severing proteins, GTPases and members of the Wnt signaling pathway were all responsible for disrupting localization. In other studies in the lab, additional organelles and proteins have been found to localize to branch points to help maintain the complex cellular organization. We hypothesize that the same machinery may be required to localize all branch point components and several mechanisms may establish the localization at this distinct cellular site. We can create a hierarchy of the candidates involved in upstream or downstream pathways to help determine the order necessary to control branch point localization and microtubule polarity.