The human synaptic vesicle protein, SV2A, functions as a galactose transporter in Saccharomyces cerevisiae

J Biol Chem. 2014 Nov 28;289(48):33066-71. doi: 10.1074/jbc.C114.584516. Epub 2014 Oct 17.


SV2A is a synaptic vesicle membrane protein expressed in neurons and endocrine cells and involved in the regulation of neurotransmitter release. Although the exact function of SV2A still remains elusive, it was identified as the specific binding site for levetiracetam, a second generation antiepileptic drug. Our sequence analysis demonstrates that SV2A has significant homology with several yeast transport proteins belonging to the major facilitator superfamily (MFS). Many of these transporters are involved in sugar transport into yeast cells. Here we present evidence showing, for the first time, that SV2A is a galactose transporter. We expressed human SV2A in hexose transport-deficient EBY.VW4000 yeast cells and demonstrated that these cells are able to grow on galactose-containing medium but not on other fermentable carbon sources. Furthermore, the addition of the SV2A-binding antiepileptic drug levetiracetam to the medium inhibited the galactose-dependent growth of hexose transport-deficient EBY.VW4000 yeast cells expressing human SV2A. Most importantly, direct measurement of galactose uptake in the same strain verified that SV2A is able to transport extracellular galactose inside the cells. The newly identified galactose transport capability of SV2A may have an important role in regulating/modulating synaptic function.

Keywords: Drug Action; Galactose; Levetiracetam; SV2A; Saccharomyces cerevisiae; Sugar Transport; Synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / pharmacology
  • Biological Transport, Active / physiology
  • Galactose / metabolism*
  • Humans
  • Levetiracetam
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Piracetam / analogs & derivatives
  • Piracetam / pharmacokinetics
  • Piracetam / pharmacology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Sequence Homology, Amino Acid
  • Synapses / genetics
  • Synapses / metabolism


  • Anticonvulsants
  • Membrane Glycoproteins
  • Monosaccharide Transport Proteins
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SV2A protein, human
  • Levetiracetam
  • Galactose
  • Piracetam