The Yu laboratory seeks to understand the molecular and structural basis of paracellular epithelial transport and its regulation. Paracellular transport refers to transport in between cells. It is now well-recognized that paracellular transport is a major route for vectorial transport of solutes and water. The rate-limiting step in paracellular transport (the paracellular "barrier") is constituted by the tight junctions, which consist of large complexes of multiple different proteins. The claudins are a novel family of tight junction membrane proteins that are postulated to form paracellular ion channels. Thus, claudins are likely to be structurally and biophysically different from any known ion channels. There are 27 different claudin isoforms, raising the exciting possibility that isoform-specific expression may be responsible for the variability in paracellular permeability properties of different epithelial tissues. Investigation of claudin physiology promises to reveal novel insights into the pathogenesis of diseases such as acute kidney injury, salt-sensitive hypertension and polycystic kidney disease.
Li J*, Zhuo M, Pei L*, Yu ASL. Conserved aromatic residue confers cation selectivity in claudin-2 and claudin-10b. J Biol Chem, 2013;288(31):22790-7.
Li J*, Angelow S†, Linge A, Zhuo M, Yu ASL. Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines. Am J Physiol Cell Physiol, 2013;305(2):C190-6.
Li J*, Zhuo M, Pei L*, Rajagopal M†, Yu ASL. Comprehensive cysteine-scanning mutagenesis reveals claudin-2 pore-lining residues with different intrapore locations. J Biol Chem, 289: 6475-84, 2014.
Weber C, Liang GH, Wang Y, Das S, Lingaraju A, Shen L, Yu ASL, Nelson D, Turner J. Claudin-2 dependent paracellular pores are dynamically gated. eLife 2015;10.7554/e9906
Pei L*, Solis G, Nguyen MT, Kamat N, Magenheimer L, Zhuo M, Li J, Curry J, McDonough AA, Fields TA, Welch WJ, Yu ASL. Paracellular epithelial sodium transport maximizes energy efficiency in the kidney. J Clin Invest, 2016;126: 2509-18.
*Graduate student. †Postdoctoral fellow.
Full list of Dr. Yu's publications: