N-ethylmaleimide sensitive fusion protein

N-ethylmaleimide-sensitive factor, also known as NSF or N-ethylmaleimide sensitive fusion proteins, is an is_associated_with::enzyme which in humans is encoded by the NSF is_associated_with::gene.

Function
NSF is a homohexameric AAA is_associated_with::ATPase involved in membrane fusion. NSF is ubiquitously found in the is_associated_with::cytoplasm of eukaryotic cells. It is a central component of the cellular machinery in the transfer of membrane vesicles from one membrane compartment to another. During this process, is_associated_with::SNARE proteins on two joining membranes (usually a vesicle and a target membrane such as the is_associated_with::plasma membrane) form a tight complex. This aids fusion of the vesicle with the target membrane. It has been proposed that the role of NSF is to undo these SNARE complexes once membrane fusion has occurred, using the hydrolysis of ATP as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion. This proposal remains controversial, however. Recent work indicates that the ATPase function of NSF does not function in recycling of vesicles but rather functions in the act of fusing vesicles with the plasma membrane.

SNARE hypothesis
Because neuronal function depends on the release of is_associated_with::neurotransmitters at a is_associated_with::synapse — a process in which is_associated_with::synaptic vesicles fuse with the presynaptic membrane — NSF is a key synaptic component. Thus, conditional temperature-sensitive is_associated_with::mutations in the is_associated_with::Drosophila melanogaster gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked. In is_associated_with::Dictyostelium discoideum amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration. Another neuronal role for NSF is indicated by its direct binding to the GluR2 subunit of AMPA type is_associated_with::glutamate receptors (which detect the neurotransmitter is_associated_with::glutamate). This gives NSF a putative role in delivery and expression of AMPA receptors at the is_associated_with::synapse.

NSF was discovered by is_associated_with::James Rothman and colleagues in 1987 while at is_associated_with::Stanford University; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with N-ethylmaleimide. This assay enabled them to purify NSF.

Interactions
N-ethylmaleimide sensitive fusion protein has been shown to interact with NAPA.