Trends in Cell Biology
ForumNSF—fusion and beyond
Section snippets
The AMPA receptor
The AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate) glutamate receptor[16]resides in the postsynaptic membrane, where it acts in fast-excitatory synaptic transmission of the central nervous system. The receptor is part of the postsynaptic density, which is a specialization of the cytoskeleton and positioned at the cytoplasmic face of the postsynaptic membrane[17]. Each AMPA receptor consists of multiple subunits (GluR1 through GluR4), which can produce differently composed receptors
Does NSF cheat on SNAREs?
Other lines of evidence support the idea that NSF resides in the postsynaptic density and plays an important role there. First, NSF is enriched within isolated postsynaptic density material[20], particularly after transient cerebral ischemia (Ref. [21], confirmed in Ref. [15]). Second, long-term potentiation (LTP) is inhibited by N-ethylmaleimide, which also inhibits NSF[1], and addition of recombinant SNAP increases excitatory postsynaptic currents (EPSCs)[22]. Third, NSF and GluR2 colocalize
So, why is NSF on the postsynaptic side?
The above studies suggest that NSF and SNAPs can build `20S-complex-like structures' with non-SNARE receptors and that these structures are readily disassembled by ATP hydrolysis on NSF. It therefore seems likely that the AMPA receptor and the SNARE disassembly complex have similar modes of action. This would imply that the SNAP–NSF interaction would act on GluR2 in a chaperone-like priming reaction8, 9, 11, 24, and this priming would be required continuously for receptor function. Experimental
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