PP2A-PR72: Interactions with β[Heavy]-Spectrin and Investigation of Roles in Apical Polarity and Endosomal Trafficking
Open Access
- Author:
- Travor, Mark D
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Graham Hugh Thomas, Thesis Supervisor
Dr. Michael Axtell, Thesis Honors Advisor - Keywords:
- Actin
Cytoskeleton
Drosophila
Spectrin
PP2A - Abstract:
- Spectrins are best known as cytoskeletal scaffolding proteins, but current thinking indicates that spectrin and related proteins have other crucial roles in many cell processes. Previous studies in Drosophila melanogaster have suggested a model in which the interaction between βHeavy-spectrin (βH) and the B’’ subunit of the essential Ser/Thr phosphatase PP2A (PP2A-PR72) appears to play a number of important roles. These include regulation of cell polarity determination and the trafficking of cellular components. The direct interaction of βH and PP2A at the βH C-terminus is thought to be crucial for the proper function of these pathways. Immunofluorescence experiments in embryos suggest that the interaction between PP2A and βH is dynamic: the amount of colocalization changes across development. As βH localization is constant, this change in colocalization suggests that the role of PP2A is changing. Further elucidation of the association between PP2A and βH provides validation for the hypothesis that βH scaffolds PP2A, and that the two are interdependent. Genetic interactions of βH and PP2A in salivary glands indicate a codependency between the proteins to dictate endomembrane maturation. PP2A may be responsible for activating AnxB9 removal of βH from internalized vesicles at the early endosome stage. Subcellular localization of PP2A to compartments positive for Carnation, a marker of large multivesicular late-endosomes and lysosomes, further indicates that PP2A may also be involved in AnxB9-dependent, βH-positive endosomal trafficking events. Further study of the relationship between PP2A and βH, as well as between these and other proteins, is needed to flesh out details and make more inclusive models. The evidence presented in this thesis supports a new model in which PP2A is widely associated with endosomal compartments and only acts with βH at specific times and places in the endomembrane system.