Claudins form size-and charge-selective pores in the tight junction that control the
paracellular flux of inorganic ions and small molecules. However, the structural basis for ion
selectivity of paracellular pores is poorly understood. Here we applied cysteine scanning to
map the paracellular pathway of ion permeation across claudin-2-transfected Madin-Darby
canine kidney type I cells. Four potential pore-lining amino acid residues in the first
extracellular loop were mutated to cysteine and screened for their accessibility to thiol …