Student Author(s)

Kevin Catalfano, Hope College

Faculty Mentor(s)

Dr. Leah A. Chase, Biochemistry

Document Type


Event Date



The Chase lab studies System xc-, which is a heterodimeric transporter that functions as a Na+-independent antiporter exchanging extracellular cystine for intracellular glutamate. The transporter functions as an obligate heterodimer and is comprised of two proteins, xCT, which functions specifically in amino acid exchange, and 4F2HC, which appears to play a role in transporter stability. System xc- belongs to the SLC7 family of transporters, which is further subdivided into the cationic amino acid transporters (CAT) and the L-type amino acid transporters (LAT), the latter of which is the subfamily which includes System xc-. In recent years, there have been advances in our understanding of the structure of the SLC7 transporters as crystal structures of bacterial homologs of CAT and LAT transporters have been published. As a result, we can now begin to ask important questions about the mechanism by which System xc- exchanges cystine and glutamate across the membrane. Previous studies in the Chase lab have demonstrated that System xc- is a Cl--dependent transporter that transports cystine and glutamate in their anionic form. This substrate specificity is novel among the SLC7 family of transporters, therefore, the goal of this study is to identify the amino acids within xCT that are important in Cl--binding and substrate binding and exchange. Previous studies have suggested that Cys 327 is important for transport activity and this residue is also conserved in the bacterial homolog. Therefore, we selected amino acids near cysteine 327 and within the apparent binding pocket for mutagenesis. Primers were designed to create the point mutations at S326A, T195A, F322A, Y149A, S322A, V141S and M331A, and we intend to test these mutants for transport activity. We hypothesize that mutants which lead to diminished transport activity or changes in substrate affinity are likely to be important in Cl--binding, substrate binding and/or translocation.


This research is supported by Schaap Endowed Funds for Undergraduate Research.

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Biochemistry Commons