"Cations as Molecular Switches for Junctional Adhesion Molecule-A"

Abstract

Junctional adhesion molecules (JAMs) are key structural and functional cell adhesion components of tight junctions (TJs). Cadherins (CADs), in the AJ and JAM-A in the TJ are calcium-dependent adhesion molecules. The expression of JAM-A in cells exposed to different ionic microenvironments led us to hypothesize that other cations may play a role in its function. A cation-binding site algorithm was used to identified calcium, copper, iron, magnesium, and zinc potential binding sites in JAM-A. In this article, we use recombinant protein and biophysical methods to study the effects of these cations on JAM-A. We present evidence suggesting these cations play key roles in regulating JAM-A secondary, tertiary, and quaternary structure, and cell adhesion properties.

Consequences of Immunoglobulin Domain-Containing Protein Retro-Proteins

“…Because rJAMA was already aggregated beyond the SEC sensitivity we could not confirm the effects of Zinc. JAMA's susceptibility to Zinc was reported by our group previously [37]. Using ZetaView we have confirmed that rJAMA is not dependent on Zinc.…”

“…Figure 5A demonstrates through SEC profiles how JAMA and rJAMA soluble domains behave in solution. JAMA is expected to behave mostly as a monomer in the absence of environmental factors present at the tight junction where it can form dimers and other levels of aggregation [36][37][38]. Examining the SEC profiles in Figure 5A, we observe a contrast between monomeric JAMA and multimeric rJAMA.…”

“…Nevertheless, JAM-A is involved in a variety of biological processes. Recently we have presented evidence that JAMA is calcium sensitive [36] and further more its aggregation can be triggered by cations, with the greatest effect being triggered by Zinc [37].…”