Date of Award
Master of Science (MS)
Cellular, Molecular and Biomedical Sciences
Alzheimer’s disease (AD), the most prevalent neurodegenerative disease, is characterized in part by disruptions in axonal transport. Axonal transport is a process by which motor proteins carry organelles and other cargo made in the neuronal cell body along microtubule tracks to distal regions of the axon. The microtubule-associated protein (MAP) Tau plays a crucial role in regulating axonal transport, and is implicated in the development of AD and other types of dementia collectively known as Tauopathies. Tau is a neuronal-specific MAP that has six isoforms alternatively spliced from a single gene. These isoforms differ by the presence of zero, one, or two N-terminal acidic inserts and three or four C-terminal microtubule binding repeats. Tau is also known to be an intrinsically disordered protein that undergoes a dynamic equilibrium between static and diffusive states on the microtubule surface. The dynamics of Tau are important in the regulation of motor protein mediated axonal transport in neurons. Isoform-specific differences in the dynamic behavior of Tau on the microtubule surface, however, are not yet fully understood. Diffusive Tau is thought to be stabilized by electrostatic interactions between its N- and C-termini while static Tau is proposed to be extended with its C-terminal repeats contacting the microtubule and the N-terminus projected away from the microtubule surface. Thus, the N-terminal inserts may help regulate Tau’s dynamic behavior and function during axonal transport. In this study, the dynamics of two different isoforms of Tau, both with three-microtubule binding repeats but a different number of N-terminal acidic inserts, were assessed using single molecule imaging techniques and novel data analysis methods.
Number of Pages
Redmond, Miranda, "The Role Of N-Terminal Acidic Inserts On The Dynamics Of The Tau Protein." (2017). Graduate College Dissertations and Theses. 758.
Available for download on Sunday, May 05, 2019