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 neurotransmitter glutamate. We used the two-hybrid genetic selection system in yeast to look for interactors of glutaminase in human brain. We have identified two proteins containing PDZ domains, alpha1-syntrophin and a glutaminase-interacting protein, named GIP, that showed association with human glutaminase L, as deduced from specificity test of the two-hybrid system. The complete GIP cDNA clone has 1315 nucleotides with a 372-base open reading frame encoding a 124-amino acids protein. Glutaminase associates with both PDZ proteins through its C-terminal end; mutagenesis of single amino acids revealed the sequence -ESXV as essential for the interaction. These data suggest the possibility that PDZ domain-containing proteins are involved in the regulation of glutaminase in brain.