PMID:25526735

Citation	Gill, I, Droubi, S, Giovedi, S, Fedder, KN, Bury, LA, Bosco, F, Sceniak, MP, Benfenati, F and Sabo, SL (2015) Presynaptic NMDA receptors - dynamics and distribution in developing axons in vitro and in vivo. J. Cell. Sci. 128:768-80
Abstract	During cortical development, N-methyl-D-aspartate (NMDA) receptors (NMDARs) facilitate presynaptic terminal formation, enhance neurotransmitter release and are required in presynaptic neurons for spike-timing-dependent long-term depression (tLTD). However, the extent to which NMDARs are found within cortical presynaptic terminals has remained controversial, and the sub-synaptic localization and dynamics of axonal NMDARs are unknown. Here, using live confocal imaging and biochemical purification of presynaptic membranes, we provide strong evidence that NMDARs localize to presynaptic terminals in vitro and in vivo in a developmentally regulated manner. The NR1 and NR2B subunits (also known as GRIN1 and GRIN2B, respectively) were found within the active zone membrane, where they could respond to synaptic glutamate release. Surprisingly, NR1 also appeared in glutamatergic and GABAergic synaptic vesicles. During synaptogenesis, NR1 was mobile throughout axons - including growth cones and filopodia, structures that are involved in synaptogenesis. Upon synaptogenic contact, NMDA receptors were quickly recruited to terminals by neuroligin-1 signaling. Unlike dendrites, the trafficking and distribution of axonal NR1 were insensitive to activity changes, including NMDA exposure, local glutamate uncaging or action potential blockade. These results support the idea that presynaptic NMDARs play an early role in presynaptic development.
Links	PubMed PMC4327389 Online version:10.1242/jcs.162362
Keywords	Animals; Axons/metabolism; Cell Adhesion Molecules, Neuronal/metabolism; Cells, Cultured; Dendrites/metabolism; Excitatory Postsynaptic Potentials/physiology; HEK293 Cells; Humans; Image Processing, Computer-Assisted; Microscopy, Confocal; Neurotransmitter Agents/metabolism; Presynaptic Terminals/metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate/metabolism; Receptors, Presynaptic/metabolism; Signal Transduction; Synaptic Transmission/physiology; Synaptic Vesicles/metabolism; Visual Cortex/embryology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
RAT:NMDZ1	part_of	GO:0045202: synapse	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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