File(s) under embargo

Reason: Material has been submitted to a peer-review journal. We request a hold on publishing the dissertation until the peer-reviewed article is published

941

days

21

hours

until file(s) become available

Microtubule Assembly and Translocation Dynamics During Axonal Elongation

thesis
posted on 25.06.2020 by Kristi McElmurry

The urgency for deeper knowledge about nervous system function and dysfunction has never been greater. With increasing rates of mental disorders and expanding healthcare costs, deciphering details of axonal development is essential to meeting this imperative. Models of neuronal growth are improving as roles of microtubules and motor proteins surface. However, traditional motor protein studies focus on intracellular cargo transport, leaving deficits in knowledge about how these proteins organize cytoskeletal filaments in the axon and growth cone during neuronal development. Inconsistent findings on microtubule activity in growing axons also leave gaps in quantitative assessments of microtubule translocation and assembly, limiting the ability to construct a comprehensive model of axonal elongation.

The goal of this study was to provide a more complete neuronal growth cone model by determining how individual microtubule translocation and assembly, mass microtubule movements, and motor protein activity contribute to axonal elongation. The underlying mechanisms of these processes were investigated by testing the roles of dynein and microtubule dynamics in axonal elongation of Aplysia californica neurons using transillumination, fluorescent speckle, and super-resolution microscopy. Pharmacologically inhibiting either dynein activity or microtubule assembly reduced both bulk and individual microtubule anterograde translocation and neurite elongation rates. Suppressing both processes simultaneously had compensatory rather than additive effects. Super-resolution imaging also revealed fewer dynein motors co-localized with microtubules when microtubule assembly was inhibited. These results strongly suggest that disrupting microtubule assembly blocks neurite outgrowth partly because it inhibits dynein-mediated bulk microtubule translocation.

Funding

NSF 1146944-IOS

History

Degree Type

Doctor of Philosophy

Department

Biological Sciences

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Daniel Suter

Additional Committee Member 2

Dr. Peter Hollenbeck

Additional Committee Member 3

Dr. R. Claudio Aguilar

Additional Committee Member 4

Dr. Fang Huang

Licence

Exports