Date of Award

Spring 2020

Thesis Type

Open Access

Degree Name

Honors Bachelor of Arts

Department

Biology

Sponsor

Dr. Jay Pieczynski

Committee Member

Dr. Brendaliz Santiago-Narvaez

Committee Member

Dr. Pamela Brannock

Abstract

Our nervous system propagates signals by releasing neurotransmitters into the synaptic cleft between two adjacent neurons. The transport and delivery of such neurotransmitters within the neuron is reliant on microtubule structure and motor proteins present. The direction of motor protein transport is dictated by the inherent polarity of microtubules. Kinesin-3 motor proteins, such as KLP-4 found in Caenorhabditis elegans, use this polarity to travel in an anterograde direction towards neurotransmitter exocytosis sites. Thus, KLP-4 is associated with the maintenance of neuron functionality. The klp-4 (ok3537) allele results in a large, in frame deletion within the cargo-binding domain of the motor protein, causing unknown molecular consequences. C. elegans containing this allele experience difficulty moving in reverse and disorganized synapses. Cargo that binds to the KLP-4 cargo-binding region is unknown. By tagging both wild type and mutant KLP-4 with a Myc tag, we planned to isolate and identify the proteins bound to the cargo binding domain. Additionally, in the presence of mutant KLP-4, the microtubules it travels on experience an increase in acetylation. Microtubule acetylation stabilizes microtubules and helps motor proteins travel efficiently. We suspect the combination of both functional alpha tubulin acetyltransferases, such as MEC-17 and ATAT-2, and mutant KLP-4, which signals for excess microtubule acetylation, results in the disorganized synapses associated with klp-4 (ok3537). We hypothesize that producing an organism homozygous for both the klp-4 (ok3537) allele and a knockout acetyltransferase allele, either mec-17 (ok2109) or atat-2 (ok2415), we would rescue of the mutant KLP-4 phenotype.

Rights Holder

Lindsey Wright

Available for download on Monday, May 01, 2023

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