Deletion of v7-3 (SLC6A15) transporter allows assessment of its roles in synaptosomal proline uptake, leucine uptake and behaviors

Jana Drgonova, Qing Rong Liu, F. Scott Hall, Rachael M. Krieger, George R. Uhl

Research output: Contribution to journalArticle

Abstract

v7-3 (SLC6A15) is the prototype for a gene subfamily whose members have sequence homologies to classical Na+- and Cl--dependent neurotransmitter transporters but display unusual features that include characteristic large fourth extracellular loops. Interest in v7-3 has been increased by the elucidation of its expression in neurons located in cerebral cortex, hippocampus, cerebellum, midbrain and olfactory bulb. To help clarify the role of v7-3 in brain functions, we have created and characterized v7-3 knockout mice. These mice lack functional v7-3 protein but are viable and fertile. While our studies were in progress, v7-3 expression was reported to confer transport of proline and branched-chain amino acids in in vitro expression systems [Takanaga, H., Mackenzie, B., Peng, J.B., Hediger, M.A., 2005b. Characterization of a branched-chain amino-acid transporter SBAT1 (SLC6A15) that is expressed in human brain. Biochem. Biophys. Res. Commun. 337, 892-900; Broer, A., Tietze, N., Kowalczuk, S., Chubb, S., Munzinger, M., Bak, L.K., Broer, S., 2006. The orphan transporter v7-3 (slc6a15) is a Na+-dependent neutral amino acid transporter (B0AT2). Biochem. J. 393, 421-430]. Assessment of amino acid uptake into cortical synaptosomes of v7-3 knockouts identified 15% and 40% reductions in sodium-dependent proline and leucine transport, respectively, compared to wild type controls. Despite these biochemical changes, v7-3 knockout mice demonstrate only modest alterations in rotarod performance with aging and lack reproducible alterations in other motor, memory, anxiety or olfactory tests. Compensation for the lack of v7-3 via other amino acid carriers is likely to leave v7-3 knockouts without gross behavioral manifestations. The current results place v7-3 in the context of other brain transporters that accumulate proline and branched-chain amino acids.

Original languageEnglish (US)
Pages (from-to)10-20
Number of pages11
JournalBrain Research
Volume1183
Issue number1
DOIs
StatePublished - Dec 5 2007
Externally publishedYes

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Branched Chain Amino Acids
Proline
Leucine
Knockout Mice
Brain
Neutral Amino Acid Transport Systems
Neurotransmitter Transport Proteins
Amino Acid Transport Systems
Amino Acids
Orphaned Children
Synaptosomes
Olfactory Bulb
Sequence Homology
Mesencephalon
Cerebral Cortex
Cerebellum
Hippocampus
Anxiety
Sodium
Neurons

Keywords

  • BAT2
  • Orphan neurotransmitter transporter
  • SBAT1
  • v7-3 knockout

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Deletion of v7-3 (SLC6A15) transporter allows assessment of its roles in synaptosomal proline uptake, leucine uptake and behaviors. / Drgonova, Jana; Liu, Qing Rong; Hall, F. Scott; Krieger, Rachael M.; Uhl, George R.

In: Brain Research, Vol. 1183, No. 1, 05.12.2007, p. 10-20.

Research output: Contribution to journalArticle

Drgonova, Jana ; Liu, Qing Rong ; Hall, F. Scott ; Krieger, Rachael M. ; Uhl, George R. / Deletion of v7-3 (SLC6A15) transporter allows assessment of its roles in synaptosomal proline uptake, leucine uptake and behaviors. In: Brain Research. 2007 ; Vol. 1183, No. 1. pp. 10-20.
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