Author ORCID Identifier

0009-0001-8600-842X

Date of Award

Fall 12-17-2024

Degree Type

Closed Thesis

Degree Name

Bachelor of Science (BS)

Department

Chemistry

First Advisor

Daniel N. Cox

Abstract

Ribosomes are a key component of the protein homeostasis (proteostasis) network that controls protein synthesis, folding, and degradation, driving functional diversity and nervous system complexity. Proteostasis maintenance is challenging in neurons due to their unique morphology, which directly impacts neural connectivity and signal propagation. The importance of neuronal architecture in regulating nervous system function is highlighted by proteinopathic diseases and other neurological disorders that stem from dendritogenesis dysfunction.

Historically, ribosomes were thought to be homogenous machinery, but recent studies have instead suggested the concept of “specialized ribosomes,” which posits that ribosomes preferentially translate select mRNAs based on several factors, such as ribosome composition in different cell types. However, the mechanistic role of ribosome heterogeneity in regulating dendritic morphology remains unknown. Dissecting the impact of specialized ribosomes on morphology and neuronal function could be key to understanding disorders linked to ribosomal dysfunction, such as autism and microcephaly.

To address this, our lab previously conducted cell-type-specific morphological screening of thirty ribosomal proteins (RPs) in CI and CIV neurons in Drosophila melanogaster. Individual RPs were knocked down using the GAL4/UAS binary system, and the results showed that, while most knockdown affected dendritic morphology in both classes, select RP knockdown had a cell-type-specific effect. The effect of RP knockdown on ribosome localization along the dendritic arbor and at branch points was also investigated. Our results suggest that knockdown of RPs that disrupt dendritic morphology also causes defects in ribosome trafficking, indicating a cell-type specific requirement of RPs in maintaining neuronal architecture.

To determine the putative effects of ribosome heterogeneity on global protein translation, fluorescent non-canonical amino acid tagging (FUNCAT) was performed. When combined with cell-type-specific gene expression, FUNCAT allows for class-specific protein visualization and quantitative analysis of protein translation. Additionally, a preliminary ribosomal protein conservation study was performed to determine if certain ribosomal proteins are functionally conserved across species.

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