Abstract

Astrocytes are an abundant subclass of glial cells that perform diverse functions critical to development, maintenance and survival of the central nervous system. Within one of its territories, an astrocyte may influence synaptic physiology by secreting soluble molecules, uptake extracellular neurotransmitter from a synaptic cleft, or promote the formation and/or elimination of the thousands of synapses. To do so, these cells express specific proteins, receptors and ion channels in specialized sub-compartments, termed ԰erisynaptic processes.ՠRegulation of spatial gene expression in these processes has yet to be investigated. Devastating neurodegenerative disorders such as amyotrophic lateral sclerosis result in dysregulation of at least one perisynaptic-localized gene product, indicating the importance of proper gene expression in astrocytes. Here, I demonstrate for the first time that astrocytes locally synthesize proteins in their perisynaptic processes. I posit that local synthesis of protein is a mechanism used by astrocytes to interact with thousands of synapses simultaneously. I discovered hundreds of differentially expressed perisynaptic mRNAs bound to astrocyte ribosomes and use these data to investigate the mechanism of mRNA regulation in astrocytes. I found that Quaking RNA binding protein plays a significant role in regulation of astrocyte transcripts, particularly one that controls synaptogenesis. Lastly, I explore how astrocyte translation is regulated by neuronal activity and reveal non-cell autonomous mechanisms governing translational programs in the astrocyte. Together this study reveals a novel mechanism in astrocytes, and investigates the role of a specific RNA binding protein regulates these transcripts, ultimately lending insight, for the first time, to spatial gene expression regulation in astrocytes.

Committee Chair

Joseph D. Dougherty

Committee Members

Kelly R. Monk, Steven Mennerick, Barak A. Cohen, Michael Wong,

Comments

Permanent URL: 2019-07-23

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Summer 8-15-2018

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-5840-5148

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Available for download on Monday, August 15, 2118

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