Dopamine Transporter Tryptophan Mutants Highlight Candidate Dopamine- and Cocaine-Selective Domains

Lin et al. 58 (6): 1581 -- Molecular Pharmacology: "Dopamine transport has been modeled as involving a number of discrete steps likely to involve many different domains of the DAT protein. These could include sodium, dopamine, and chloride recognition by an 'outward facing' transporter state, dopamine and ion translocation, intracellular unloading of dopamine and ions, and return of the unloaded carrier to its extracellular-facing state (Povlock and Schenk, 1997). DAT's turnover rate for dopamine could be influenced by mutations that altered any of these processes. Interestingly, dopamine turnover was altered by a higher fraction of the normally expressed DAT tryptophan mutants, 43%, than the fraction at which mutations alter affinities for either dopamine or CFT. Proline, phenylalanine, and aspartic acid mutant series also displayed prominent alterations in turnover number: 41% of phenylalanine substitutions display turnover number changes, although the maximal magnitude of the change is larger for the phenylalanine mutants "

Man, I wish I could figure out what all of that meant! :)