The C-terminus is critical for the functional expression of the human serotonin transporter.

Abstract:

:The plasma membrane serotonin transporter (SERT) has an important role in terminating serotonergic neurotransmission by re-uptake of 5-HT from the synaptic cleft. The expression of SERT on the cell surface is therefore a critical factor. In this study, we examined the role of the carboxyl terminus of SERT in trafficking to the plasma membrane. 5-HT uptake activity was used to measure the effects of systematic deletions or alanine substitutions in the C-terminus. We found that deletion of 16 amino acids in the distal C-terminus had no effect on uptake activity, whereas further deletion was detrimental for the function of SERT. Cell surface biotinylation was used to determine the role of the C-terminus in localization and trafficking. We showed that the C-terminus is crucial for the delivery of SERT to the plasma membrane and that the deletion of this part of the transporter results in a lack of mature glycosylation and impaired trafficking to the plasma membrane. Furthermore, the C-terminally truncated mutants were shown to have a dominant negative effect on wild-type SERT uptake activity.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Larsen MB,Fjorback AW,Wiborg O

doi

10.1021/bi0508688

subject

Has Abstract

pub_date

2006-01-31 00:00:00

pages

1331-7

issue

4

eissn

0006-2960

issn

1520-4995

journal_volume

45

pub_type

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