Cellular functions of NSF: Not just SNAPs and SNAREs

Abstract 

N-ethylmaleimide sensitive factor (NSF) is an ATPases associated with various cellular activities protein (AAA), broadly required for intracellular membrane fusion. NSF functions as a SNAP receptor (SNARE) chaperone which binds, through soluble NSF attachment proteins (SNAPs), to SNARE complexes and utilizes the energy of ATP hydrolysis to disassemble them thus facilitating SNARE recycling. While this is a major function of NSF, it does seem to interact with other proteins, such as the AMPA receptor subunit, GluR2, and β2-AR and is thought to affect their trafficking patterns. New data suggest that NSF may be regulated by transient post-translational modifications such as phosphorylation and nitrosylation. These new aspects of NSF function as well as its role in SNARE complex dynamics will be discussed.

Abbreviations: NSF, N-ethylmaleimide sensitive factor, AAA, ATPases associated with various cellular activities, SNAP, soluble NSF attachment protein, SNARE, SNAP receptor, VAMP, vesicle associated membrane protein, TMD, transmembrane domain, AMPAR, α-amino-5-hydroxy-3-methyl-4-isoxazole propionic acid receptor, GluR2, glutamate receptor 2, GABA, γ-amino-butyric acid, GBR, GABA_B receptor, β2-AR, β2-adrenergic receptor, GPCR, G-protein coupled receptor, CRLR, calcitonin receptor-like receptor, RAMP, receptor activity-modifying proteins, AM, adrenomedullin, NMJ, neuromuscular junction, PKC, protein kinase C, PTP, protein tyrosine phosphatase, GATE-16, Golgi-associated ATPase enhancer of 16kDa, VCP, valosin containing protein, Rip11/Gaf-1, Rab interaction protein 11/γ-SNAP associated factor 1, EEA-1, early endosome antigen 1, SRH, second region of homology, LMA1, low molecular weight activity 1, GEC1, glandular epithelial cell 1

Keywords: NSF, SNARE, α-SNAP, GluR2, β2-AR, Post-translational modification