Urea Transport Mediated by Membrane Proteins of Non-urea-Transporters

Urea is generated by the urea cycle enzymes, which are mainly in the liver but are also ubiquitously expressed at low levels in other tissues of mammals. Urea is then eliminated through fluids, especially urine. Urea also serves as a readily available nitrogen source for the growth of many organisms, including plants and bacteria. Urea transporters are recognized as the primary membrane proteins responsible for urea transport in organisms. However, an increasing body of studies has identified additional membrane proteins in animals, plants, and microbes that exhibit urea transport capabilities or potential. The contribution of these membrane proteins to the maintenance of physiological homeostasis and their interactions with urea transporters remains to be fully elucidated. In this chapter, transport, characteristics, regulation, as well as cellular localization of non-urea-transporter membrane proteins facilitating urea transport, are reviewed to highlight their roles in physiology and pathophysiology. Specifically, the mammalian aquaporins AQP3, AQP6, AQP7, AQP8, AQP9, AQP10, and a sodium-glucose transporter (SGLT1) in the kidney are permeable to urea. In plants, tonoplast intrinsic proteins (TIPs), a member of aquaporin family, and the DUR3 orthologue, potentially play roles in low- and high-affinity urea transport, respectively. Two urea transporters pH-independent (Yut) and pH-dependent transporters (ureI) in bacteria are known to play roles in disease conditions.