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A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility
Author(s) -
Siksou Léa,
Silm Kätlin,
Biesemann Christoph,
Nehring Ralf B.,
Wojcik Sonja M.,
Triller Antoine,
El Mestikawy Salah,
Marty Serge,
Herzog Etienne
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12199
Subject(s) - synaptic vesicle , vesicular transport protein , neurotransmitter , glutamate receptor , excitatory postsynaptic potential , biology , neuroscience , vesicle , biochemistry , central nervous system , inhibitory postsynaptic potential , receptor , membrane
Synaptic vesicles ( SV s) from excitatory synapses carry vesicular glutamate transporters ( VGLUT s) that fill the vesicles with neurotransmitter. Although the essential function of VGLUT s as glutamate transporters has been well established, the evidence for additional cell‐biological functions is more controversial. Both VGLUT 1 and VGLUT 2 disruptions in mice result in a reduced number of SV s away from release sites, flattening of SV s, and the appearance of tubular structures. Therefore, we analysed the morphology, biochemical composition and trafficking of SV s at synapses of VGLUT 1 −/− mice in order to test for a function of VGLUT s in the formation or clustering of SV s. Analyses with high‐pressure freezing immobilisation and electron tomography pointed to a role of VGLUT 1 transport function in the tonicity of excitatory SV s, explaining the aldehyde‐induced flattening of SV s observed in VGLUT 1 −/− synapses. We confirmed the steep reduction in the number of SV s previously observed in VGLUT 1 −/− presynaptic terminals, but did not observe accumulation of endocytotic intermediates. Furthermore, SV proteins of adult VGLUT 1 −/− 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 SV s. Synaptobrevin2–enhanced green fluorescent protein time lapse experiments revealed an oversized superpool of SV s in VGLUT 1 −/− neurons. Our results support the idea that, beyond glutamate loading, VGLUT 1 enhances the tonicity of excitatory SV s and stabilises SV s at presynaptic terminals.