How the kidney handles chloride reabsorption has long been a mystery. Here, Jianghui Hou, PhD, and his colleagues have discovered a pathway in the kidney that utilizes channel-activating protease 1 and claudin-4 to physiologically regulate tight junction permeability to chloride.
Such a pathway not only is important in renal regulation of chloride but also may play key roles in chloride transport across many other epithelia such as the lung, the salivary gland, and the skin.
This discovery also attests to a concept of “druggable” tight junction. Proteases or protease-dependent mechanisms may be developed as pharmacological tools to transiently regulate tight junction permeability in the kidney, the intestine, and the blood–brain barrier. Read more in the Proceedings of the National Academy of Sciences.