Disease relevance of comt

• In addition, the entire vesicle pool can be depleted in shibire comatose double mutants, demonstrating that NSF activity is not required for the fusion step itself [1].
• The NSF transcript is present in components of the central nervous system, including the brain, SG, thoracic ganglion and abdominal ganglion, but is not present in nonneural tissues [2].

Psychiatry related information on comt

• In contrast, stimulation of presynaptic inputs to the giant fiber (referred to as the "long latency pathway") revealed a striking difference between wild type and comt at 36 degrees C. Repetitive stimulation of the long latency pathway led to a progressive, activity-dependent increase in the response latency in comt, but not in wild type [3].

High impact information on comt

• The precise biochemical role of N-ethylmaleimide-sensitive factor (NSF) in membrane fusion mediated by SNARE proteins is unclear [4].
• A well-charaterized NSF mutant containing an inactivating point mutation in the catalytic site of its ATPase domain is equally active in the Golgi-reassembly assay [4].
• A subsequent ATPase-independent NSF activity restricted to the reassembly phase is essential for membrane fusion [5].
• NSF/alpha-SNAP catalyze the binding of GATE-16 to GOS-28, a Golgi v-SNARE, in a manner that requires ATP but not ATP hydrolysis [5].
• Genetic-interaction studies with para demonstrate that blocking evoked fusion delays the accumulation of assembled SNARE complexes and behavioral paralysis that normally occurs in comatose mutants, indicating NSF activity is not required in the absence of vesicle fusion [1].

Biological context of comt

• Both extragenic enhancers result in TS behavioral phenotypes when separated from comt, and both map to loci not previously identified in screens for TS mutants [6].
• Here we report the isolation and analysis of four mutations that modify TS paralysis in comt, including two intragenic modifiers (one enhancer and one suppressor) and two extragenic modifiers (both enhancers) [6].
• We now report the identification of a second homolog of NSF, called dNSF-2 within this species and report evidence that this ubiquitous and widely utilized fusion protein belongs to a multigene family [7].
• The intragenic mutations will contribute to structure-function analysis of dNSF1 and the extragenic mutations identify gene products with related functions in synaptic transmission [6].
• N-ethylmaleimide sensitive fusion protein (NSF) is an ATPase necessary for vesicle trafficking, including exocytosis [8].

Anatomical context of comt

• To define dNSF1 function further, we used transmission electron microscopy to examine the distribution of vesicles within synaptic terminals, and observed a marked accumulation of docked vesicles at restrictive temperatures in comt [9].
• N-Ethylmaleimide-sensitive fusion protein (NSF) is an ATPase known to have an essential role in intracellular membrane transport events [7].
• Our previous work with temperature-sensitive (TS) paralytic alleles of comt has revealed a function for dNSF1 at synapses, where it appears to prime synaptic vesicles for neurotransmitter release [6].
• Interestingly, while dNSF-1 also translocates in comt(TP7) larvae, there is no associated neurophysiological phenotype at the neuromuscular junction (nmj) or accumulation of SDS-resistant complexes in the CNS [10].
• The N-ethylmaleimide-sensitive fusion protein (NSF) has been implicated in vesicle trafficking in perhaps all eukaryotic cells [6].

Associations of comt with chemical compounds

• Analysis of the mutant Drosophila N-ethylmaleimide sensitive fusion-1 protein in comatose reveals molecular correlates of the behavioural paralysis [10].
• Fusion of vesicles with target membranes is dependent on the interaction of target (t) and vesicle (v) SNARE (soluble NSF (N-ethylmaleimide-sensitive fusion protein) attachment protein receptor) proteins located on opposing membranes [11].
• Both products possess corresponding sequences for longin domain at N-terminus, a soluble N-ethylmaleimide-sensitive factor [NSF] attachment protein receptor (SNARE) coiled-coil region, a transmembrane domain (TM), and an intravesicular tail C-terminal, characteristics of all long VAMPs or longins [12].

Physical interactions of comt

• Analysis of NSF mutants reveals residues involved in SNAP binding and ATPase stimulation [13].

Other interactions of comt

• However, the most recently isolated cac mutant was identified as an enhancer of a comatose mutation's effects on general locomotion [14].
• The N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP) are cytosolic factors that promote vesicle fusion with a target membrane in both the constitutive and regulated secretory pathways [15].
• Altogether, these data support the idea that diverse NSF2 developmental and physiological phenotypes are related to disruption of the cytoskeleton and the large number of genes which can partially restore NMJ overgrowth and suggests that NSF may function near the top of the actin regulatory pathway. genesis 44:595-600, 2006 [16].

Analytical, diagnostic and therapeutic context of comt

• We show that larval clusters are Golgi stack precursors by 1) localizing various Golgi-specific markers to the larval clusters by electron and immunofluorescence confocal microscopy, 2) driving this conversion in wild-type larvae incubated at 37 degrees C for 2 h, and 3) showing that this conversion does not take place in an NSF1 mutant (comt 17) [17].
• A novel member of the NSF family in the corn earworm, Helicoverpa zea: molecular cloning, developmental expression, and tissue distribution [2].

References