What we do...

Our research is aimed at obtaining a better understanding the molecular, cellular, and physiological properties of ENTs and their relationships to each other and other nucleoside metabolic (e.g. enzymes) and signaling (e.g. receptors) proteins. Recent studies in ENT1 and ENT2 knockout mice and identification of human disorders linked to mutations in ENT3 (a subcellular isoform) suggests that these proteins are important in cellular homeostasis and human health. The most evolutionarily divergent isoforms, ENT4 (PMAT) transports both adenosine and organic cations such as serotonin and its physiological role in cells and tissues remains unclear.

Nucleoside Transporters

Our research program focuses on one class of solute transporters, the ENTs (SLC29), which are present in virtually all eukaryotic cells. ENTs are integral membrane proteins, whose structure, function and regulation remain poorly understood. Four ENT isoforms (ENT1-4) have been identified in mammals and they are broadly distributed taxonomically but have no bacterial homolog. NTs play an important role in various clinical settings; as the route of entry of anti-cancer, anti-viral drugs and anti-parasitic nucleoside analog drugs and as the targets of drugs used in various cardiomyopathies.

Membrane Proteins

The boundary of a cell is highly dynamic region. The intracellular cytoplasm, just beneath the plasma membrane, consists of a complex array of structural proteins supporting, for instance, intracellular and membrane-bound proteins involved in signaling or flux. Extracellularly, most cells are continually bathed in a complex soup of nutrients, secreted products such as hormones, and metabolic by-products form both internal and external environment. The plasma membrane is an active interface which separates these two worlds while allowing dynamic communication and exchange due to the presence of a rich assortment of channels, pumps, transporters and receptors.

Putative topology of hENT1.

hENT1 is a 456 aa membrane protein with 11 predicted transmembrane domains (TMD), a short intracellular N-terminus, a short extracellular C-terminus and a large unstructured intracellular loop between TMD 6 and 7. hENT1 is predicted to be glycosylated at N48 (first extracellular loop). A number of potential regulatory sites have been identified in the loop between TMD 6 and 7 including putative kinase consensus sites.