The density of small tight junction pores varies among cell types and is increased by expression of claudin-2

作者：Christina M. Van Itallie, Jennifer L. Holmes, Arlene S. Bridges, Jody L. Gookin, Maria R. Coccaro, William R. Proctor, Oscar R. Colegio, James Melvin Anderson · 发表于：Journal of Cell Science · 年份：2008 · DOI：10.1242/jcs.021485 · 被引用次数：412 · 研究领域：Barrier Structure and Function Studies、Neurological Disease Mechanisms and Treatments、Connexins and lens biology

Epithelial tight junctions contain size- and charge-selective pores that control the paracellular movement of charged and noncharged solutes. Claudins influence the charge selectivity and electrical resistance of junctions, but there is no direct evidence describing pore composition or whether pore size or density differs among cell types. To characterize paracellular pores independent of influences from charge selectivity, we profiled the ;apparent permeabilities' (P(app)) of a continuous series of noncharged polyethylene glycols (PEGs) across monolayers of five different epithelial cell lines and porcine ileum. We also characterized P(app) of high and low electrical resistance MDCK cell monolayers expressing heterologous claudins. P(app) profiling confirms that the paracellular barrier to noncharged solutes can be modeled as two distinct pathways: high-capacity small pores and a size-independent pathway allowing flux of larger solutes. All cell lines and ileum share a pore aperture of radius 4 A. Using P(app) of a PEG of radius 3.5 A to report the relative pore number provides the novel insight that pore density along the junction varies among cell types and is not necessarily related to electrical resistance. Expression of claudin-2 results in a selective increase in pore number but not size and has no effect on the permeability of PEGs that are larger than the pores; however, neither knockdown of claudin-2 nor overexpression of several other claudins altered either the nu...