Electronic Theses and Dissertations

Date of Award

2017

Document Type

Dissertation

Degree Name

M.S. in Chemistry

Department

Chemistry and Biochemistry

First Advisor

Susan D. Pedigo

Second Advisor

Davita Watkins

Third Advisor

Murrell Godfrey

Relational Format

dissertation/thesis

Abstract

Cadherins are the primary transmembrane component in adherens junctions, structures that link the actin cytoskeleton in adjacent cells within solid tissues including neurological synapses, epithelium and endothelium. Cell-cell adhesion by cadherins requires the binding of calcium ions to specific sites in the extracellular region. Given the complexity of the cell adhesion microenvironment, we are investigating whether other divalent cations might affect calciumdependent dimerization of neural-(N-) cadherin. The first chapter focuses on studies to characterize the impact of binding physiological magnesium (II) or neurotoxic nickel (II) on calcium-dependent N-cadherin function. Physiological levels of magnesium have only a small effect on the calcium-binding affinity and calcium-induced dimerization of N-cadherin. However, a tenfold lower concentration of nickel decreases the apparent calcium-binding affinity and calcium-induced dimerization of N-cadherin. Competitive binding studies indicate that the apparent dissociation constants for nickel and magnesium are 0.2 mM and 2.5 mM, respectively. These Kd values are consistent with concentrations observed for a range of divalent cations in the extracellular space. Results from these studies indicate that calcium-induced dimerization by Ncadherin is attenuated by natural and non-physiological divalent cations in the extracellular microenvironment. The second chapter will detail my contributions to studies into the effect of pH on the structure and function of neural cadherin that utilize many of the same analytical techniques.

Included in

Biochemistry Commons

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