Gene Symbol: comt
Description: comatose
Alias: CG 1618, CG1618, Comt, DmNSF, Dmel\CG1618, NSF, NSF-1, NSF1, Nsf, com, dNSF, dNSF-1, dNSF1, dNsf1, dnsf1, comatose, CG1618-PA, CG1618-PB, N-ethyl-maleimide sensitive fusion protein, N-ethylmaleimide-sensitive fusion protein, NEM-sensitive fusion protein, comt-PA, comt-PB
Species: fruit fly

Top Publications

  1. Morgan A. Classic clues to NSF function. Nature. 1996;382:680 pubmed
  2. Johnson E, Ringo J, Dowse H. Modulation of Drosophila heartbeat by neurotransmitters. J Comp Physiol B. 1997;167:89-97 pubmed
    ..Dopamine-N-acetyltransferase, which is on the catabolic route to dopamine, serotonin, and octopamine, has no effect. hypoactiveC reduces the rate of the heart, but its mechanism of action is unknown. ..
  3. Golby J, Tolar L, Pallanck L. Partitioning of N-ethylmaleimide-sensitive fusion (NSF) protein function in Drosophila melanogaster: dNSF1 is required in the nervous system, and dNSF2 is required in mesoderm. Genetics. 2001;158:265-78 pubmed
    ..function in many eukaryotes, previous work has shown that the Drosophila genome contains two distinct NSF genes, dNSF1 and dNSF2, raising the possibility that each plays a specific secretory role...
  4. Mohtashami M, Stewart B, Boulianne G, Trimble W. Analysis of the mutant Drosophila N-ethylmaleimide sensitive fusion-1 protein in comatose reveals molecular correlates of the behavioural paralysis. J Neurochem. 2001;77:1407-17 pubmed
    ..dNSF-1 is encoded by the gene comatose (comt), first identified as the locus of a temperature-sensitive paralytic mutation...
  5. Siddiqi O, Benzer S. Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1976;73:3253-7 pubmed
    A new temperature-sensitive paralytic mutant of Drosophila, comatose, is compared behaviorally and physiologically with the previously known types, para and shi...
  6. Tolar L, Pallanck L. NSF function in neurotransmitter release involves rearrangement of the SNARE complex downstream of synaptic vesicle docking. J Neurosci. 1998;18:10250-6 pubmed
    ..We have addressed this issue by using the temperature-sensitive Drosophila NSF mutant comatose (comt) to study the function of NSF in neurotransmitter release in vivo...
  7. Kawasaki F, Mattiuz A, Ordway R. Synaptic physiology and ultrastructure in comatose mutants define an in vivo role for NSF in neurotransmitter release. J Neurosci. 1998;18:10241-9 pubmed
    ..mutations in a Drosophila NSF gene, dNSF1, are responsible for the temperature-sensitive paralytic phenotype in comatose (comt) mutants...
  8. Littleton J, Chapman E, Kreber R, Garment M, Carlson S, Ganetzky B. Temperature-sensitive paralytic mutations demonstrate that synaptic exocytosis requires SNARE complex assembly and disassembly. Neuron. 1998;21:401-13 pubmed
    ..Temperature-sensitive paralytic mutations in NSF (comatose) also block synaptic transmission, but over a much slower time course and with the accumulation of syntaxin and ..
  9. Pallanck L, Ordway R, Ramaswami M, Chi W, Krishnan K, Ganetzky B. Distinct roles for N-ethylmaleimide-sensitive fusion protein (NSF) suggested by the identification of a second Drosophila NSF homolog. J Biol Chem. 1995;270:18742-4 pubmed
    ..We previously cloned a neurally expressed Drosophila homolog, dNSF-1 (Ordway, R.W., Pallanck, L., and Ganetzky, B. (1994) Proc. Natl. Acad. Sci. U.S.A...

More Information


  1. Kawasaki F, Ordway R. Molecular mechanisms determining conserved properties of short-term synaptic depression revealed in NSF and SNAP-25 conditional mutants. Proc Natl Acad Sci U S A. 2009;106:14658-63 pubmed publisher
    ..synaptic vesicle trafficking implicate a core complex of proteins comprised of N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs in synaptic vesicle fusion and neurotransmitter release...
  2. Rieckhof G, Yoshihara M, Guan Z, Littleton J. Presynaptic N-type calcium channels regulate synaptic growth. J Biol Chem. 2003;278:41099-108 pubmed
    ..Linking presynaptic voltage-gated calcium entry to downstream calcium-sensitive synaptic growth regulators provides an efficient activity-dependent mechanism for modifying synaptic strength. ..
  3. Palladino M, Hadley T, Ganetzky B. Temperature-sensitive paralytic mutants are enriched for those causing neurodegeneration in Drosophila. Genetics. 2002;161:1197-208 pubmed
    ..Further studies of vacu and the other neurodegenerative mutants isolated should ultimately help dissect the biochemical pathways leading to neurodegeneration. ..
  4. Littleton J, Barnard R, Titus S, Slind J, Chapman E, Ganetzky B. SNARE-complex disassembly by NSF follows synaptic-vesicle fusion. Proc Natl Acad Sci U S A. 2001;98:12233-8 pubmed
    ..To determine where in the synaptic-vesicle cycle NSF functions, we have undertaken a genetic analysis of comatose (dNSF-1) in Drosophila...
  5. Linial M, Parnas D. Deciphering neuronal secretion: tools of the trade. Biochim Biophys Acta. 1996;1286:117-52 pubmed
  6. Babcock M, Macleod G, Leither J, Pallanck L. Genetic analysis of soluble N-ethylmaleimide-sensitive factor attachment protein function in Drosophila reveals positive and negative secretory roles. J Neurosci. 2004;24:3964-73 pubmed
    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...
  7. Swaffield J, Purugganan M. The evolution of the conserved ATPase domain (CAD): reconstructing the history of an ancient protein module. J Mol Evol. 1997;45:549-63 pubmed that lead to the establishment of different functional AAA proteins, including proteasomal regulatory, NSF/Sec, and Pas proteins...
  8. Rikhy R, Kamat S, Ramagiri S, Sriram V, Krishnan K. Mutations in dynamin-related protein result in gross changes in mitochondrial morphology and affect synaptic vesicle recycling at the Drosophila neuromuscular junction. Genes Brain Behav. 2007;6:42-53 pubmed
    ..These data, in addition to depletion of vesicles observed in electron microscopic sections of photoreceptor synapses at restrictive temperatures, suggest a block in synaptic vesicle recycling due to reduced mitochondrial function. ..
  9. Littleton J, Pallanck L, Ganetzky B. Mechanisms of neurotransmitter release. Int Rev Neurobiol. 1999;43:139-61 pubmed
  10. Freeman A, Bowers M, Mortimer A, Timmerman C, Roux S, Ramaswami M, et al. A new genetic model of activity-induced Ras signaling dependent pre-synaptic plasticity in Drosophila. Brain Res. 2010;1326:15-29 pubmed publisher
    ..Here, we demonstrate activity-induced plasticity at neuromuscular synapses of Drosophila double mutant for comatose (an NSF mutant) and Kum (a SERCA mutant), and present an analysis of the underlying signaling pathways...
  11. Yu W, Kawasaki F, Ordway R. Activity-dependent interactions of NSF and SNAP at living synapses. Mol Cell Neurosci. 2011;47:19-27 pubmed publisher
    ..This work employs a temperature-sensitive (TS) paralytic NSF mutant, comatose, to show that disruption of NSF function results in activity-dependent redistribution of NSF and SNAP to ..
  12. Homyk T, Pye Q. Some mutations affecting neural or muscular tissues alter the physiological components of the electroretinogram in Drosophila. J Neurogenet. 1989;5:37-48 pubmed
    ..Mutations bas, rex and sesD delay recovery from the prolonged depolarization afterpotential. The visual defects of mutations elavjl and nbAEE171 are not complemented by lethal mutations, which, presumably, affect other tissues. ..
  13. Freeman A, Franciscovich A, Bowers M, Sandstrom D, Sanyal S. NFAT regulates pre-synaptic development and activity-dependent plasticity in Drosophila. Mol Cell Neurosci. 2011;46:535-47 pubmed publisher
    ..We propose that NFAT regulates pre-synaptic development and constrains long-term plasticity by dampening neuronal excitability. ..
  14. Stimson D, Estes P, Rao S, Krishnan K, Kelly L, Ramaswami M. Drosophila stoned proteins regulate the rate and fidelity of synaptic vesicle internalization. J Neurosci. 2001;21:3034-44 pubmed
    ..These observations are consistent with a model in which stonedA and stonedB act to facilitate the internalization of synaptic vesicle components from the plasma membrane. ..
  15. Wang P, Saraswati S, Guan Z, Watkins C, Wurtman R, Littleton J. A Drosophila temperature-sensitive seizure mutant in phosphoglycerate kinase disrupts ATP generation and alters synaptic function. J Neurosci. 2004;24:4518-29 pubmed
    ..Both exocytotic (NSF) and endocytotic (dynamin) ATPase/GTPase activity are required for normal synaptic transmission...
  16. Ganetzky B. Genetic studies of membrane excitability in Drosophila: lethal interaction between two temperature-sensitive paralytic mutations. Genetics. 1984;108:897-911 pubmed
    ..These results together with previous electrophysiological, behavioral and pharmacological studies of these mutants suggest that both para and nap affect sodium channels and possibly encode different subunits. ..
  17. Li T, Tian Y, Li Q, Chen H, Lv H, Xie W, et al. The Neurexin/N-Ethylmaleimide-sensitive Factor (NSF) Interaction Regulates Short Term Synaptic Depression. J Biol Chem. 2015;290:17656-67 pubmed publisher
    ..two-hybrid screen, we find that the intracellular region of NRX interacts with N-ethylmaleimide-sensitive factor (NSF), an enzyme that mediates soluble NSF attachment protein receptor (SNARE) complex disassembly and plays an ..
  18. Uytterhoeven V, Lauwers E, Maes I, Miskiewicz K, Melo M, Swerts J, et al. Hsc70-4 Deforms Membranes to Promote Synaptic Protein Turnover by Endosomal Microautophagy. Neuron. 2015;88:735-48 pubmed publisher
  19. Gokhale A, Mullin A, Zlatic S, Easley C, Merritt M, Raj N, et al. The N-ethylmaleimide-sensitive factor and dysbindin interact to modulate synaptic plasticity. J Neurosci. 2015;35:7643-53 pubmed publisher neuroectodermal cells and iPSC-derived human neurons, among them the N-ethylmaleimide-sensitive factor (NSF)...
  20. Hoeffer C, Sanyal S, Ramaswami M. Acute induction of conserved synaptic signaling pathways in Drosophila melanogaster. J Neurosci. 2003;23:6362-72 pubmed
  21. Parfitt K, Reist N, Li J, Burgess R, Deitcher D, DiAntonio A, et al. Drosophila genetics and the functions of synaptic proteins. Cold Spring Harb Symp Quant Biol. 1995;60:371-7 pubmed
  22. Horsnell W, Steel G, Morgan A. Analysis of NSF mutants reveals residues involved in SNAP binding and ATPase stimulation. Biochemistry. 2002;41:5230-5 pubmed intracellular membrane traffic in vivo is highlighted by the inhibition of neurotransmission in Drosophila comatose (NSF) mutants and of constitutive secretion in yeast sec18 mutants...
  23. Babcock D, Ganetzky B. Transcellular spreading of huntingtin aggregates in the Drosophila brain. Proc Natl Acad Sci U S A. 2015;112:E5427-33 pubmed publisher
    ..Finally we show that the release of aggregates requires N-ethylmalemide-sensitive fusion protein 1, demonstrating that active release and uptake of Htt aggregates are important elements of spreading and disease progression. ..
  24. Chan B, Villella A, Funes P, Hall J. Courtship and other behaviors affected by a heat-sensitive, molecularly novel mutation in the cacophony calcium-channel gene of Drosophila. Genetics. 2002;162:135-53 pubmed
    ..However, the most recently isolated cac mutant was identified as an enhancer of a comatose mutation's effects on general locomotion...
  25. Richmond J, Broadie K. The synaptic vesicle cycle: exocytosis and endocytosis in Drosophila and C. elegans. Curr Opin Neurobiol. 2002;12:499-507 pubmed
    ..In neuromodulation, dcaps mutants provide the first genetic insight into possible roles of the CAPS protein in mediating dense core vesicle fusion and modulating synaptic vesicle fusion. ..
  26. Lilly M, Kreber R, Ganetzky B, Carlson J. Evidence that the Drosophila olfactory mutant smellblind defines a novel class of sodium channel mutation. Genetics. 1994;136:1087-96 pubmed
    ..Two sbl mutations produce olfactory defects not characteristic of classic sodium channel mutations and do not show typical heat-sensitive paralysis, suggesting that these sbl mutants define a novel class of sodium channel mutation. ..
  27. Dunne J, Kondylis V, Rabouille C. Ecdysone triggers the expression of Golgi genes in Drosophila imaginal discs via broad-complex. Dev Biol. 2002;245:172-86 pubmed
    ..we show here that ecdysone triggers the upregulation of a subset of genes encoding Golgi-related proteins (such as dnsf1, dsec23, dsed5, and drab1) and downregulates the expression of others (such as dergic53, dbeta'COP, and drab6)...
  28. Krishnan K, Rikhy R, Rao S, Shivalkar M, Mosko M, Narayanan R, et al. Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron. 2001;30:197-210 pubmed
    ..This connection between NDK and membrane internalization further strengthens an emerging hypothesis that endocytosis, probably of activated growth factor receptors, is an important tumor suppressor activity in vivo. ..
  29. Ordway R, Pallanck L, Ganetzky B. Neurally expressed Drosophila genes encoding homologs of the NSF and SNAP secretory proteins. Proc Natl Acad Sci U S A. 1994;91:5715-9 pubmed
    ..of two types of cytosolic proteins thought to function in this complex: N-ethylmaleimide-sensitive fusion protein (NSF) and the soluble NSF attachment proteins (SNAPs)...
  30. Babcock D, Shen W, Ganetzky B. A neuroprotective function of NSF1 sustains autophagy and lysosomal trafficking in Drosophila. Genetics. 2015;199:511-22 pubmed publisher
    ..Here we show that one of these mutants, comatose (comt), in addition to locomotor defects, displays shortened lifespan and progressive neurodegeneration, ..
  31. Majumdar A, Ramagiri S, Rikhy R. Drosophila homologue of Eps15 is essential for synaptic vesicle recycling. Exp Cell Res. 2006;312:2288-98 pubmed
    ..Genetic and biochemical studies of interactions with components of the endocytic machinery suggest that Eps15 has an important role in synaptic vesicle recycling and regulates recruitment of alpha-Adaptin. ..
  32. Sanyal S, Krishnan K. Lethal comatose mutation in Drosophila reveals possible role for NSF in neurogenesis. Neuroreport. 2001;12:1363-6 pubmed
    ..Here we report a lethal mutation in the Drosophila homolog of NSF (dNSF1)...
  33. Wu M, Bellen H. Genetic dissection of synaptic transmission in Drosophila. Curr Opin Neurobiol. 1997;7:624-30 pubmed
    ..In addition, characterization of Drosophila endocytotic mutants provides in vivo evidence for the presence of different endocytotic pathways at a single synapse. ..
  34. Kawasaki F, Collins S, Ordway R. Synaptic calcium-channel function in Drosophila: analysis and transformation rescue of temperature-sensitive paralytic and lethal mutations of cacophony. J Neurosci. 2002;22:5856-64 pubmed
    ..Possible implications of these findings are discussed in the context of structure-function studies of synaptic calcium channels, as well as alternative splicing and mRNA editing of the cac transcript. ..
  35. Huang F, Woodruff E, Mohrmann R, Broadie K. Rolling blackout is required for synaptic vesicle exocytosis. J Neurosci. 2006;26:2369-79 pubmed
    ..We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion. ..
  36. Seugnet L, Galvin J, Suzuki Y, Gottschalk L, Shaw P. Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease. Sleep. 2009;32:984-92 pubmed
    ..These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics. ..
  37. Homyk T, Szidonya J, Suzuki D. Behavioral mutants of Drosophila melanogaster. III. Isolation and mapping of mutations by direct visual observations of behavioral phenotypes. Mol Gen Genet. 1980;177:553-65 pubmed
  38. Dellinger B, Felling R, Ordway R. Genetic modifiers of the Drosophila NSF mutant, comatose, include a temperature-sensitive paralytic allele of the calcium channel alpha1-subunit gene, cacophony. Genetics. 2000;155:203-11 pubmed
    ..The Drosophila comatose (comt) gene encodes an NSF homolog, dNSF1...
  39. Sanyal S, Krishnan K. Genetic modifiers of comatose mutations in Drosophila: insights into neuronal NSF (N-ethylmaleimide-sensitive fusion factor) functions. J Neurogenet. 2012;26:348-59 pubmed publisher
    ..experiments led to the isolation of a number of conditional mutations including shibire, paralytic, and comatose. All have since been cloned and have enabled deep mechanistic insights into synaptic transmission and nerve ..
  40. Kondylis V, Goulding S, Dunne J, Rabouille C. Biogenesis of Golgi stacks in imaginal discs of Drosophila melanogaster. Mol Biol Cell. 2001;12:2308-27 pubmed
    ..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)...
  41. Adolfsen B, Saraswati S, Yoshihara M, Littleton J. Synaptotagmins are trafficked to distinct subcellular domains including the postsynaptic compartment. J Cell Biol. 2004;166:249-60 pubmed
    ..In addition, the identification of a postsynaptic synaptotagmin suggests calcium-dependent membrane-trafficking functions on both sides of the synapse. ..
  42. Krishnan K, Chakravarty S, Rao S, Raghuram V, Ramaswami M. Alleviation of the temperature-sensitive paralytic phenotype of shibire(ts) mutants in Drosophila by sub-anesthetic concentrations of carbon dioxide. J Neurogenet. 1996;10:221-38 pubmed
    ..s. paralytic phenotype of hypoactive parats flies defective in axonal voltage-gated sodium channels. ..
  43. Pallanck L, Ordway R, Ganetzky B. A Drosophila NSF mutant. Nature. 1995;376:25 pubmed
  44. Muller J, Shorter J, Newman R, Deinhardt K, Sagiv Y, Elazar Z, et al. Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion. J Cell Biol. 2002;157:1161-73 pubmed
    Characterization of mammalian NSF (G274E) and Drosophila NSF (comatose) mutants revealed an evolutionarily conserved NSF activity distinct from ATPase-dependent SNARE disassembly that was essential for Golgi membrane fusion...
  45. Boulianne G, Trimble W. Identification of a second homolog of N-ethylmaleimide-sensitive fusion protein that is expressed in the nervous system and secretory tissues of Drosophila. Proc Natl Acad Sci U S A. 1995;92:7095-9 pubmed
    ..Recently, cDNA clones encoding a Drosophila melanogaster homolog of this protein, named dNSF, were characterized and found to be expressed in the nervous system...
  46. Bate M, Broadie K. Wiring by fly: the neuromuscular system of the Drosophila embryo. Neuron. 1995;15:513-25 pubmed
  47. Schotman H, Karhinen L, Rabouille C. dGRASP-mediated noncanonical integrin secretion is required for Drosophila epithelial remodeling. Dev Cell. 2008;14:171-82 pubmed publisher
    ..We speculate that this mechanism might be used during development as a means of targeting a specific subset of transmembrane proteins to the plasma membrane. ..
  48. Sanyal S, Basole A, Krishnan K. Phenotypic interaction between temperature-sensitive paralytic mutants comatose and paralytic suggests a role for N-ethylmaleimide-sensitive fusion factor in synaptic vesicle cycling in Drosophila. J Neurosci. 1999;19:RC47 pubmed
    The temperature-induced paralysis of comatose (comt) mutants of Drosophila is suggestive of a function for N-ethylmaleimide-sensitive fusion factor (NSF) in the CNS...
  49. Xu H, Mohtashami M, Stewart B, Boulianne G, Trimble W. Drosophila SNAP-29 is an essential SNARE that binds multiple proteins involved in membrane traffic. PLoS ONE. 2014;9:e91471 pubmed publisher
    ..Overexpression and RNAi studies suggested that dSNAP-29 mediates an essential process in Drosophila development. ..
  50. Lagow R, Bao H, Cohen E, Daniels R, Zuzek A, Williams W, et al. Modification of a hydrophobic layer by a point mutation in syntaxin 1A regulates the rate of synaptic vesicle fusion. PLoS Biol. 2007;5:e72 pubmed