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Author ORCID Identifier

https://orcid.org/0000-0003-1223-7120

AccessType

Open Access Dissertation

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2021

Month Degree Awarded

September

First Advisor

Margaret Stratton

Second Advisor

Scott Garman

Third Advisor

Peter Chien

Fourth Advisor

Luke Chao

Subject Categories

Biochemistry | Biophysics | Molecular Biology

Abstract

Long-term memory and learning are still poorly understood from a molecular and cellular standpoint. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is an oligomeric kinase that is involved in this remarkable process. However, the molecular details of its specific roles in these processes remains elusive. CaMKII activation-triggered subunit exchange presents a novel possible mechanism involved in long-term memory and learning by exchanging active subunits with other CaMKIIs. CaMKII subunit exchange also shows that exchanged CaMKIIs spread their phosphorylation state to newly synthesized CaMKIIs. This provides a long-lasting signal that might possibly be involved in long-term memory by escaping a cell’s protein turnover. In this thesis work, I expanded understanding of CaMKII activation-triggered subunit exchange to the other CaMKII human genes, CaMKIIγ and CaMKIIδ. I also characterized CaMKIIα holoenzyme stability. I also uncovered a potential new role for CaMKII oligomerization and how it is related to activation properties. Lastly, I used CaMKII FRET biosensor Camui for a proof of concept using microscopy technology FLIM-FRET.

DOI

https://doi.org/10.7275/24533941

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Available for download on Thursday, September 01, 2022

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