title: Nicotinamide mononucleotide adenylyltransferase maintains active zone structure by stabilizing Bruchpilot.
abstract: Active zones are specialized presynaptic structures critical for neurotransmission. We show that a neuronal maintenance factor, nicotinamide mononucleotide adenylyltransferase (NMNAT), is required for maintaining active zone structural integrity in Drosophila by interacting with the active zone protein, Bruchpilot (BRP), and shielding it from activity-induced ubiquitin-proteasome-mediated degradation. NMNAT localizes to the peri-active zone and interacts biochemically with BRP in an activity-dependent manner. Loss of NMNAT results in ubiquitination, mislocalization and aggregation of BRP, and subsequent active zone degeneration. We propose that, as a neuronal maintenance factor, NMNAT specifically maintains active zone structure by direct protein-protein interaction.
authors.affiliation: Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
authors.forename: Shaoyun
authors.initials: S
authors.lastname: Zang
authors.forename: Yousuf O
authors.initials: YO
authors.lastname: Ali
authors.forename: Kai
authors.initials: K
authors.lastname: Ruan
authors.forename: R Grace
authors.initials: RG
authors.lastname: Zhai
mesh_terms: D000818:Animals; D004330:Drosophila / Q000201:enzymology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C510146:BRP protein, Drosophila; D029721:Drosophila Proteins; D034741:RNA, Small Interfering; D025801:Ubiquitin; D009612:Nicotinamide-Nucleotide Adenylyltransferase; D046988:Proteasome Endopeptidase Complex