The C-terminus of human glutaminase L mediates association with PDZ domain-containing proteins

The enzyme glutaminase in brain is responsible for the synthesis of neurotr ansmitter glutamate, We used the two-hybrid genetic selection system in yea st to look for interactors of glutaminase in human brain. We have identifie d two proteins containing PDZ domains, alpha1-syntrophin and a glutaminase- interacting protein, named GIP, that showed association with human glutamin ase L, as deduced from specificity test of the two-hybrid system. The compl ete GIP cDNA clone has 1315 nucleotides with a 372-base open reading frame encoding a 124-amino acids protein. Glutaminase associates with both PDZ pr oteins through its C-terminal end; mutagenesis of single amino acids reveal ed the sequence -ESXV as essential for the interaction. These data suggest the possibility that PDZ domain-containing proteins are in, ol, ed in the r egulation of glutaminase in brain. (C) 2001 Federation of European Biochemi cal Societies.