A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking.
Regulated exocytosis is essential for many biological processes and many components of the protein trafficking machinery are ubiquitous. However, there are also exceptions, such as SNAP-25, a neuron-specific SNARE protein that is essential for synaptic vesicle release from presynaptic nerve terminals. In contrast, SNAP-23 is a ubiquitously expressed SNAP-25 homolog that is critical for regulated exocytosis in non-neuronal cells. However, the role of SNAP-23 in neurons has not been elucidated. We found that SNAP-23 was enriched in dendritic spines and colocalized with constituents of the postsynaptic density, whereas SNAP-25 was restricted to axons. In addition, loss of SNAP-23 using genetically altered mice or shRNA targeted to SNAP-23 led to a marked decrease in NMDA receptor surface expression and NMDA receptor currents, whereas loss of SNAP-25 did not. SNAP-23 is therefore important for the functional regulation of postsynaptic glutamate receptors.
Suh
Young Ho
YH
Receptor Biology Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Terashima
Akira
A
Petralia
Ronald S
RS
Wenthold
Robert J
RJ
Isaac
John T R
JT
Roche
Katherine W
KW
Roche
Paul A
PA
D000818:Animals; D001369:Axons / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003712:Dendrites / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C107017:Snap23 protein, mouse; C498858:Snap23 protein, rat; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins