Date of Award

1-1-2013

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biological Sciences

Content Description

1 online resource (xi, 132 pages) : illustrations (some color)

Dissertation/Thesis Chair

Ben G. Szaro

Committee Members

Richard S. Zitomer, John T. Schmidt, Scott A. Tenenbaum

Keywords

Axon outgrowth, c-Jun N-terminal kinase, hnRNP K, Post-transcriptional regulation, RNA-binding protein, Xenopus, Axons, Xenopus laevis, RNA-protein interactions, Genetic transcription

Subject Categories

Biology | Developmental Biology | Neuroscience and Neurobiology

Abstract

The RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNP K), is required for axon outgrowth. Its suppression in Xenopus embryos causes defects in the translation of mRNAs of multiple cytoskeletal genes. Studies in cell lines have established that hnRNP K shuttles between the nucleus and the cytoplasm to bind and regulate the fates of its target RNAs, from splicing to export and translation. At each step, hnRNP K is regulated through post-translational modifications that alter its nucleic acid and protein interactions, and subcellular localization. Precisely how this happens in developing neurons to coordinate cytoskeletal gene expression with the extracellular signals directing axon outgrowth is unknown. The cellular kinase, c-Jun N-terminal Kinase (JNK), has long been implicated in the intracellular signaling pathways that mediate effects of several receptors on axon outgrowth, although a mechanism of its action had not previously been demonstrated. For my dissertation, I proposed to examine the role of JNK-mediated post-translational modification of hnRNP K on its functions in axon outgrowth.

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