Identification of a vesicular aspartate transporter
- 19 August 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (33), 11720-11724
- https://doi.org/10.1073/pnas.0804015105
Abstract
Aspartate is an excitatory amino acid that is costored with glutamate in synaptic vesicles of hippocampal neurons and synaptic-like microvesicles (SLMVs) of pinealocytes and is exocytosed and stimulates neighboring cells by binding to specific cell receptors. Although evidence increasingly supports the occurrence of aspartergic neurotransmission, this process is still debated because the mechanism for the vesicular storage of aspartate is unknown. Here, we show that sialin, a lysosomal H(+)/sialic acid cotransporter, is present in hippocampal synaptic vesicles and pineal SLMVs. RNA interference of sialin expression decreased exocytosis of aspartate and glutamate in pinealocytes. Proteoliposomes containing purified sialin actively accumulated aspartate and glutamate to a similar extent when inside positive membrane potential is imposed as the driving force. Sialin carrying a mutation found in people suffering from Salla disease (R39C) was completely devoid of aspartate and glutamate transport activity, although it retained appreciable H(+)/sialic acid cotransport activity. These results strongly suggest that sialin possesses dual physiological functions and acts as a vesicular aspartate/glutamate transporter. It is possible that people with Salla disease lose aspartergic (and also the associated glutamatergic) neurotransmission, and this could provide an explanation for why Salla disease causes severe neurological defects.Keywords
This publication has 32 references indexed in Scilit:
- Identification of a vesicular nucleotide transporterProceedings of the National Academy of Sciences, 2008
- Reduced aspartate release from rat hippocampal synaptosomes loaded with Clostridial toxin light chain by electroporation: Evidence for an exocytotic mechanismNeuroscience Letters, 2007
- Sialin, an anion transporter defective in sialic acid storage diseases, shows highly variable expression in adult mouse brain, and is developmentally regulatedNeurobiology of Disease, 2005
- Neurocognitive profiles in Salla diseaseDevelopmental Medicine and Child Neurology, 2004
- Release of d,l-threo-β-hydroxyaspartate as a false transmitter from excitatory amino acid-releasing nerve terminalsNeurochemistry International, 2001
- Glutamate uptakeProgress in Neurobiology, 2001
- p-Aminohippuric Acid Transport at Renal Apical Membrane Mediated by Human Inorganic Phosphate Transporter NPT1Biochemical and Biophysical Research Communications, 2000
- Purification of the Lysosomal Sialic Acid TransporterPublished by Elsevier BV ,1998
- Selective Activation of Calcium Permeability by Aspartate in Purkinje CellsScience, 1996
- Amino acid neurotransmission: spotlight on synaptic vesiclesTrends in Neurosciences, 1990