NSF and AMPA Receptors Get Physical

the vesicle expresses a specific membrane protein Department of Neurobiology (v-SNARE) that binds to a cognate receptor on the target Howard Hughes Medical Institute membrane (t-SNARE). For synaptic vesicle exocytosis, Massachusetts General Hospital the v-SNARE VAMP/synaptobrevin, an integral mem-and Harvard Medical School brane protein of the synaptic vesicle, interacts with the Boston, Massachusetts 02114 t-SNAREs syntaxin and SNAP-25 on the presynaptic membrane. These three proteins (the original and still the best-characterized SNAREs) can associate via coiled-Yeast two-hybrid screens can be exciting but risky fish-coil interactions in a stable ternary complex, the forma-ing expeditions. You never know if you will land a big tion of which is proposed to underlie target-specific one or pull up an old boot. Certainly, what you hook docking. NSF is recruited to this core complex via solu-with your bait can be surprising. Three recent papers in ble NSF attachment proteins (SNAPs; no relation to this and the July issue of Neuron use the two-hybrid SNAP-25) that can bind directly to the SNARE proteins system to identify N-ethylmaleimide–sensitive fusion (SNARE derives from SNAP receptor). The resulting com-protein (NSF) as a protein that binds specifically to the plex (the " 20S particle ") containing v-SNARE, t-SNAREs, cytoplasmic tail of AMPA receptor subunit GluR2 (Nishi-SNAPs, and NSF is stable only in the absence of hydro-mune et al. lyzable ATP. ATP hydrolysis by NSF dissociates the 20S [this issue of Neuron]). This interaction connects a pro-particle (Figure 1). In this sense, NSF can be regarded tein well known in vesicle fusion with an ionotropic neu-as a chaperone-like molecule that uses an ATP energy rotransmitter receptor that functions at postsynaptic source to reconfigure the tertiary/quaternary structure sites. To understand the implications of these findings, of associated proteins. This energy-dependent disas-it is necessary to introduce NSF, a protein that plays an sembly was proposed to drive fusion of the apposed essential role in membrane vesicle trafficking. v-SNARE– and t-SNARE–containing membranes. NSF and the SNARE Hypothesis Although the SNARE hypothesis was influential, spe-The trafficking of vesicles between membrane-bound cific aspects of the original model have been updated. compartments is a fundamental process that shapes the For instance, SNAREs may play a postdocking role in morphological and biochemical topology of eukaryotic membrane fusion. With regard to NSF, it now seems cells. Vesicles act as shuttles that distribute their cargo unlikely that ATP hydrolysis by NSF drives membrane (which can be membrane bound or luminal) …