Cadmium Disruption of Neural Cadherin Dimerization

Date

2019-04-30

Authors

Williams, Garrett

Access rights

Worldwide access.
Access changed 8/17/21.

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

Cadherins are calcium-dependent cell-adhesion proteins that are vital to the formation and maintenance of solid tissues. Neural (N-) Cadherin plays an essential role in early development processes such as angiogenesis and development of the neural plate. The prerequisite of calcium (Ca2+) binding for adhesion begs the question of whether other divalent cations could promote or inhibit dimer formation. Due to its ionic radius and chelation geometry, cadmium (Cd2+) has been shown to substitute for Ca2+ in select physiological processes. The studies described here evaluate whether Cd2+ binds to N-Cadherin as a heteroligand, thereby disrupting calcium-induced dimerization. Studies were also conducted to predict the effects of Cd2+ at relatively low Ca2+ concentration, as typical for excitatory neural synapses. This study features both experimental and numerical analysis of ligand binding and ligand-induced dimerization. The ligand binding constants resolved for calcium and cadmium indicated that cadmium binds to N-cadherin with ~4x higher affinity than that of calcium. Further, low levels of Cd2+ decrease dimer formation at calcium concentrations found at neurological synapses. Analysis shows that Cd2+ disrupts dimerization of N-Cadherin, consistent with its competition for the Ca2+-binding sites. Our observations of dimer disassembly in the presence of Cd2+ support the hypothesis that at very low levels, Cd2+ will have minimal effect on N-Cadherin mediated cell-adhesion in the body; however, Cd2+ at these same levels at excitatory synapses can disrupt cell adhesion and compromise normal neurological processes including the formation of memory and reflex stimulation.

Description

Keywords

Neural cadherin., Biophysics., Cell., Cell adhesion.

Citation