Antibody-based Techniques Clarify Mechanisms Regulating Epithelial Cell Migration

Mon, 01/18/2010 - 10:00

Researchers can manipulate antibodies to yield very impressive research outcomes, which may prove highly relevant to the medical treatment of the future.

Severson et al (MBC 2009, 20(7) pp. 1916-1925) used antibodies, including monoclonal rabbit anti-JAM-A and monoclonal rabbit anti-β1 integrin from Novus Biologicals to investigate epithelial cell migration.

In a previous study, this team demonstrated that cell migration is regulated by junctional adhesion molecule A. JAM-A is a transmembrane protein in tight junctions, namely areas where membranes of adjacent cells join closely together. In epithelial cells, JAM-A is thought to decrease paracellular permeability and favour epithelial cell migration. These functions maintain the barrier function of intestinal epithelium. Barrier function is compromised in some intestinal diseases. Stress can cause further dysfunction. The net result is increased uptake of harmful toxins and antigens from the intestinal lumen, leading to further exacerbation. Greater understanding of the mechanisms maintaining intestinal barrier function may identify new therapeutic strategies in intestinal disease.

The study was performed in monolayers of a human epithelial colonic cell line and in isolated colonic epithelial cells from JAM-A-deficient and control mice. The results indicated that dimerisation of JAM-A acts as a signal to regulate epithelial cell migration. The dimers interact with Afadin and PDZ-GEF2 to activate the DNA-binding protein Rap1A. This in turn stabilises β1 integrin and thus regulates cell migration.

The authors state that further studies are required to establish the mechanism by which Rap1A stabilizes β1 integrin levels in epithelial cells. It may be that antibodies to both these substances, available from the Novus Biologicals antibody catalog, will contribute to this research.

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