Glutamate-101 is critical for the function of the sodium and chloride-coupled GABA transporter GAT-1.

Abstract:

:We have investigated the possible role of selected negatively-charged amino acids of the sodium and chloride-coupled GABA transporter GAT-1 on sodium binding. These residues located adjacent to putative transmembrane domains and which are conserved throughout the large superfamily of neurotransmitter transporters were changed by site-directed mutagenesis. The functional consequences were that one of the residues, glutamate-101, was critical for transport. Its replacement by aspartate left only 1% of the activity, and no activity could be detected when it was replaced by other residues. Expression levels and targeting to the plasma membrane of the mutant transporters appeared normal. Transient sodium currents were not observed in the mutants, and increased sodium concentrations did not affect the percentage of wild type transport of the E101D mutant. It is concluded that residue glutamate-101 is critical for one or more of the conformational changes of GAT-1 during its transport cycle.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Keshet GI,Bendahan A,Su H,Mager S,Lester HA,Kanner BI

doi

10.1016/0014-5793(95)00859-8

subject

Has Abstract

pub_date

1995-08-28 00:00:00

pages

39-42

issue

1

eissn

0014-5793

issn

1873-3468

pii

0014-5793(95)00859-8

journal_volume

371

pub_type

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