Date of Award

6-14-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

School of Biological Sciences

First Advisor

Alysia V. Mortimer

Abstract

Lamins are the major components of the nuclear lamina where they provide a platform for the binding of proteins to the chromatin and confer mechanical stability (Dittmer and Misteli.,2011). Mutations in the human LMNA gene result in at least 15 distinct disorders ranging from muscular dystrophies to neurological disorders to lipodystrophies (Vytopil et al.,2003). Interestingly, some mutant forms of lamin protein aggregate, which may be toxic to the cells. However, it is unknown how specific mutations in lamin give rise to tissue-specific disease. I hypothesize that certain tissues are susceptible to specific lamin mutations due to the inability of tissue-specific quality control mechanisms to degrade those mutant forms, leading to protein aggregation and cellular toxicity. I will be testing if tissue-specific disease mutations in Lam Dm0, one of the fly homologs of LMNA (Gene that codes for Lamin), cause the protein to aggregate in muscles and neurons. Lamin can be post-translationally modified by the addition of a farnesyl group that helps anchor Lamin into the nuclear envelop. We find that the unfarnesylated form (the predominant form) and the farnesylated form of the different Lam Dm0mutant proteins have different expression patterns in the muscle. In addition, we find that the p38 MAPK (p38Kb) interacts with the CASA (Chaperone Assisted Selective Autophagy) complex to regulate the degradation of Lam Dm0. Future experiments will characterize how these mutant forms of Dm0 affect the functionality of the muscles and neurons in flies and if these forms can be targeted for degradation by p38Kb and the CASA complex.

Comments

Imported from Acquah_ilstu_0092N_12440.pdf

DOI

https://doi.org/10.30707/ETD2023.20231004061827097697.1000000

Page Count

93

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