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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2014

First Advisor

Jennifer L. Ross

Second Advisor

Maria Kilfoil

Third Advisor

Wei-Lih Lee

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Other Physics

Abstract

Intracellular transport provides a mechanism by which cellular material, such as organelles, vesicles, and protein, can be actively transported throughout the cell. This process relies on the activity of the cytoskeletal filament, microtubules, and their associated motor proteins. These motors are able to walk along microtubule tracks while carrying cellular cargos to enable the fast, regulated transport of these cargos. In cells, these microtubule filaments act as a binding platform for numerous different motor species as well as microtubule-associated proteins (MAPs). In addition, these filaments often form higher order structures, such as microtubule bundles. How motors navigate such complex, crowded tracks to ensure the efficient transport of cargos is unclear. While motor transport can be studied in vivo, such studies are complicated to interpret as there are many unknowns, such as which motor species are driving transport, which MAPs are bound to specific regions of microtubule tracks, and what types of microtubule architectures are present.

In the studies presented here, motor transport was reconstituted in vitro, allowing for the precise control over motor types, motor densities, the relative number of motors per cargo, and the types of microtubule tracks present. To this simplified system, specific complexities were added to microtubule tracks to systematically study the effect of certain track complexities on motor transport. Specifically, the effect of motor traffic and different microtubule bundle architectures on the transport properties of kinesin-1 motors was studied. In addition, the effect of motor domain mutations on the transport properties of kinesin-1 motors was also probed. These studies provide new insights into how motor transport is altered on microtubule tracks reminiscent of those present in the cell, as well as mechanisms utilized by kinesin motors to efficiently navigate these complex tracks.

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