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“Tau N-terminal Disease Associated Mutation, R5L, Alters Microtubule Mediated Behavior and Function”

February 9 @ 11:30 am - 12:30 pm

UVM Cellular, Molecular and Biomedical Sciences (CMB) Seminar 

Online 11:30 AM – 12:30 PM – Join the seminar

“Tau N-terminal Disease Associated Mutation, R5L, Alters Microtubule Mediated Behavior and Function”

Alisa Cairo

Advisor:  Christopher Berger, UVM Department of Molecular Physiology and Biophysics

Abstract

Understanding the physiological function of the intrinsically disordered microtubule associated protein (MAP) Tau has proven challenging. Tau, primarily expressed in neurons, is known to have a variety of axonal functions, including regulation of microtubule dynamics and modulation of kinesin motor motility. Misregulation of MAP-Tau has been linked to neurological diseases, such as Progressive Supranuclear Palsy. However, it is not well understood how disease associated mutations affect Tau behavior and function. The canonical theory states mutations in Tau reduce Tau affinity for the microtubule. Here, we investigate the role of an N-terminal disease associated mutation in Tau, R5L, using an in vitro reconstituted system for Total Internal Reflection Fluorescence (TIRF) Microscopy. Contrary to the canonical theory, we determined the R5L mutation does not reduce Tau affinity for the microtubule. Rather, the R5L mutation reduces the total amount of Tau bound to the microtubule at saturating conditions. Our data suggests the R5L mutation decreases the ability of Tau to form larger order complexes, known as “Tau patches”. This behavioral change in binding leads to a functional consequence. The R5L mutation reduces the ability of Tau to regulate microtubule dynamics. Currently, we are determining the mechanism by which this occurs, potentially due to a structural change associated with the R5L mutation. Altogether, these results challenge the current paradigm of how mutations in Tau lead to disease.

Details

Date:
February 9
Time:
11:30 am - 12:30 pm
Event Category: