A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility.
Eur J Neurosci. 2013-04-15; 37(10): 1631-1642
DOI: 10.1111/ejn.12199
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1. Eur J Neurosci. 2013 May;37(10):1631-42. doi: 10.1111/ejn.12199. Epub 2013 Apr
15.
A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and
mobility.
Siksou L(1), Silm K, Biesemann C, Nehring RB, Wojcik SM, Triller A, El Mestikawy
S, Marty S, Herzog E.
Author information:
(1)Institute of Biology of the Ecole Normale Supérieure, Paris, France.
Synaptic vesicles (SVs) from excitatory synapses carry vesicular glutamate
transporters (VGLUTs) that fill the vesicles with neurotransmitter. Although the
essential function of VGLUTs as glutamate transporters has been well established,
the evidence for additional cell-biological functions is more controversial. Both
VGLUT1 and VGLUT2 disruptions in mice result in a reduced number of SVs away from
release sites, flattening of SVs, and the appearance of tubular structures.
Therefore, we analysed the morphology, biochemical composition and trafficking of
SVs at synapses of VGLUT1(-/-) mice in order to test for a function of VGLUTs in
the formation or clustering of SVs. Analyses with high-pressure freezing
immobilisation and electron tomography pointed to a role of VGLUT1 transport
function in the tonicity of excitatory SVs, explaining the aldehyde-induced
flattening of SVs observed in VGLUT1(-/-) synapses. We confirmed the steep
reduction in the number of SVs previously observed in VGLUT1(-/-) presynaptic
terminals, but did not observe accumulation of endocytotic intermediates.
Furthermore, SV proteins of adult VGLUT1(-/-) mouse brain tissue were expressed
at normal levels in all subcellular fractions, suggesting that they were not
displaced to another organelle. We thus assessed the mobility of the recently
documented superpool of SVs. Synaptobrevin2-enhanced green fluorescent protein
time lapse experiments revealed an oversized superpool of SVs in VGLUT1(-/-)
neurons. Our results support the idea that, beyond glutamate loading, VGLUT1
enhances the tonicity of excitatory SVs and stabilises SVs at presynaptic
terminals.
© 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
DOI: 10.1111/ejn.12199
PMID: 23581566 [Indexed for MEDLINE]