Date Approved

11-2016

Embargo Period

5-24-2023

Document Type

Dissertation

Degree Name

PhD in Cell & Molecular Biology

Department

Graduate School of Biomedical Sciences

College

School of Osteopathic Medicine

First Advisor

Venkateswar Venkataraman, PhD

Second Advisor

Mikhail Anikin, PhD

Third Advisor

Dmitry Temiakov, PhD

Subject(s)

Neuronal Calcium-Sensor Proteins; Neurocalcin; Hippocalcin; Calcium-Binding Proteins

Disciplines

Cell Biology | Laboratory and Basic Science Research | Medicine and Health Sciences | Molecular and Cellular Neuroscience | Molecular Biology

Abstract

Many neuronal functions, including learning and memory are driven by changes in intracellular Ca2+concentrations. The Neuronal Calcium Sensor (NCS) family of proteins is responsible for mediating the response to calcium. They are typically comprised of 4 EF hands; of which EF 2, 3, and 4 bind calcium.

Hypothesis: NCS proteins carry out unique, non-overlapping functions, and that specific characteristics of the family can be mapped to precise regions of the proteins.

Results: The effect on the following properties were investigated primarily on two highly similar NCS proteins, Neurocalcin Delta (NCALD) and Hippocalcin (HPCA): (1) Response to calcium was determined through two independent methods: change in tryptophan fluorescence and migration on a native polyacrylamide gel (CIMSA); (2) size exclusion chromatography, (3) Calcium binding, (4) Guanylate Cyclase stimulations and (5) sequence analysis. These results lead to the conclusion that specific aa locations are hyper-variable and pivotal in determining how the proteins respond.

Comments

Additional committee members: Robert Nagele, PhD and Eric Moss, PhD

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