C. Sur et al., A SINGLE SERINE RESIDUE CONTROLS THE CATION DEPENDENCE OF SUBSTRATE TRANSPORT BY THE RAT SEROTONIN TRANSPORTER, Proceedings of the National Academy of Sciences of the United Statesof America, 94(14), 1997, pp. 7639-7644
The serotonin transporter (SERT) is a member of the Na+/Cl--dependent
neurotransmitter transporter family and constitutes the target of seve
ral clinically important antidepressants. Here, replacement of serine-
545 in the recombinant rat SERT by alanine was found to alter the cati
on dependence of serotonin uptake. Substrate transport was now driven
as efficiently by LiCl as by NaCl without significant changes in serot
onin affinity. Binding of the antidepressant [H-3]imipramine occurred
with 1/5th the affinity, whereas [H-3]citalopram binding was unchanged
. These results indicate that serine-545 is a crucial determinant of b
oth the cation dependence of serotonin transport by SERT and the imipr
amine binding properties of SERT.