Affordable Access

An extracellular loop region of the serotonin transporter may be involved in the translocation mechanism.

Authors
  • Stephan, M M
  • Chen, M A
  • Penado, K M
  • Rudnick, G
Type
Published Article
Journal
Biochemistry
Publication Date
Feb 11, 1997
Volume
36
Issue
6
Pages
1322–1328
Identifiers
PMID: 9063880
Source
Medline
License
Unknown

Abstract

The serotonin transporter (SERT) is a member of a highly homologous family of proteins responsible for the reuptake of biogenic amines from the synaptic cleft. We took advantage of native restriction sites in SERT to construct a chimeric transporter containing a small (34 amino acid) region of the norepinephrine transporter. The substituted region corresponds to about half of the largest extracellular loop. This chimera transports serotonin very slowly compared to wild type SERT. However, it binds serotonin and the cocaine analog 2beta-carbomethoxy-3beta-(4-[125I]iodophenyl)tropane with a high affinity indistinguishable from wild type. It has the same specificity as wild type SERT for the antidepressants paroxetine and desipramine. The low rate of transport does not appear to be due to poor expression, since the chimeric transporter is expressed at the membrane surface at close to wild type levels as measured by cell surface biotinylation. These observations lead us to conclude that, rather than playing a role in substrate or drug binding, this region of the large extracellular loop may be involved in the conformational changes associated with substrate translocation into the cell.

Report this publication

Statistics

Seen <100 times