NSF (N-ethyl-maleamide sensitive factor, also known as A0117) plays an important role in vesicle-mediated transport in the secretory and endocytic pathways.
NSF (N-ethyl-maleamide sensitive factor, also known as A0117) plays an important role in vesicle-mediated transport in the secretory and endocytic pathways. NSF exists as a hexamer and is a member of the AAA gene family (ATPases associated with diverse cellular activities). NSF binds to SNARE proteins (soluble N-ethylmaleimide-sensitive factors attachment protein receptors, a complex responsible for vesicle and target membrane fusion) and disassembles the SNARE complex for recycling. NSF has three major domains: N, D1, and D2. The N domain contains binding sites to its interacting partners; D1 and D2 both contain the AAA cassette, which are used during SNARE disassembly and hexamerization respectively. Apart from general membrane fusion, NSF has a central function in neurotransmission. NSF is expressed at high levels in the nervous system, playing a presynaptic role,involved in neurotransmitter release. NSF is also shown to bind to a number of synaptic proteins including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluR2, gamma-amino butyric acid (GABA) receptor subunit and proteins in the Rab family. It is suggested that NSF maintains AMPAR receptor surface expression by regulating AMPAR subunit trafficking. The expression of NSF and several other presynaptic proteins is differentially regulated in the prefrontal cortex of schizophrenia patients. No mouse model has been published for the gene.