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J Biol Chem, Vol. 274, Issue 16, 10731-10736, April 16, 1999
From the Department of Pharmacology, Hiroshima University School of
Dentistry, Kasumi 1-2-3, Minami-ku, Hiroshima 734, Japan
We have cloned from rat brain a family of
alternatively spliced cDNAs from a single gene, which encodes a
norepinephrine transporter (NET) having variations at the 3'-region
including both coding and noncoding regions. This produces two
transporter isoforms, rNETa and rNETb, which differ at their COOH
termini. The rNETa isoform reveals a COOH terminus homologous to human
NET and transports norepinephrine. In contrast, rNETb revealed no
detectable transport function but reduced functional expression of
rNETa when both isoforms were expressed in the same cell. Thus, rNETb
potentially functions as a dominant negative inhibitor of rNETa
activity. Co-expression of rNETb with a 
-aminobutyric acid
transporter (rGAT1), a serotonin transporter (rSERT), and a dopamine
transporter (rDAT) reduced their transport activity. No reduction was
found with the glutamate/aspartate transporter (rGLAST). Alternative RNA splicing of NET suggests a novel mechanism for the regulation of
synaptic transmission.
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