Presentation Title

Effects of Chemically Altered Tau on Microtubule Dynamics

Faculty Mentor

Cyrus Safinya

Start Date

18-11-2017 2:15 PM

End Date

18-11-2017 3:15 PM

Location

BSC-Ursa Minor 50

Session

Poster 3

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Microtubules (MT) are biological nanotubes composed of α-/β- tubulin heterodimers. MTs help cells maintain their shape and internal organization by providing mechanical support for essential functions like division and signal transduction. While healthy neuronal axons contain long, stable microtubules, the axons of patients diagnosed with Alzheimer’s disease show abnormally depolymerized microtubules. Tau is a MT-associated protein that is abundant in neuronal axons and is crucial for stabilizing microtubules and regulating microtubule-microtubule interactions. Post-translational modifications of tau, such as phosphorylation, can alter its electrostatic properties, leading to changes in Tau-MT and MT-MT interactions. Healthy cells maintain a tight regulation of tau phosphorylation, while the misregulation of tau phosphorylation has been implicated in neurodegenerative diseases. However, it remains poorly understood as to how and why altered electrostatics drive these “tauopathies”.

Our experiments use in vitro MT assemblies to study the underlying physics of tau-mediated MT interactions. In order to study these protein assemblies, we first overexpress mutated tau in bacteria to harvest and purify it. The mutation consists of replacing residues that are known targets for hyperphosphorylation in the disease state with acidic residues, mimicking the negative charge of a phosphorylated residue. We then polymerize MTs in the presence of our purified tau, allowing us to make direct structural and force measurements using x-ray scattering and microscopy techniques. These experiments should lay the groundwork for understanding the physical properties governing healthy and diseased axonal MT structures.

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Nov 18th, 2:15 PM Nov 18th, 3:15 PM

Effects of Chemically Altered Tau on Microtubule Dynamics

BSC-Ursa Minor 50

Microtubules (MT) are biological nanotubes composed of α-/β- tubulin heterodimers. MTs help cells maintain their shape and internal organization by providing mechanical support for essential functions like division and signal transduction. While healthy neuronal axons contain long, stable microtubules, the axons of patients diagnosed with Alzheimer’s disease show abnormally depolymerized microtubules. Tau is a MT-associated protein that is abundant in neuronal axons and is crucial for stabilizing microtubules and regulating microtubule-microtubule interactions. Post-translational modifications of tau, such as phosphorylation, can alter its electrostatic properties, leading to changes in Tau-MT and MT-MT interactions. Healthy cells maintain a tight regulation of tau phosphorylation, while the misregulation of tau phosphorylation has been implicated in neurodegenerative diseases. However, it remains poorly understood as to how and why altered electrostatics drive these “tauopathies”.

Our experiments use in vitro MT assemblies to study the underlying physics of tau-mediated MT interactions. In order to study these protein assemblies, we first overexpress mutated tau in bacteria to harvest and purify it. The mutation consists of replacing residues that are known targets for hyperphosphorylation in the disease state with acidic residues, mimicking the negative charge of a phosphorylated residue. We then polymerize MTs in the presence of our purified tau, allowing us to make direct structural and force measurements using x-ray scattering and microscopy techniques. These experiments should lay the groundwork for understanding the physical properties governing healthy and diseased axonal MT structures.