rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. 1994

K L Schulze, and J T Littleton, and A Salzberg, and N Halachmi, and M Stern, and Z Lev, and H J Bellen
Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030.

The mammalian homolog of the yeast Sec1p, n-Sec1/Munc-18 has been demonstrated to bind the presynaptic membrane protein syntaxin, a putative synaptic vesicle docking protein. To determine the role of n-Sec1/Munc-18 in neurotransmitter release in vivo, we have overexpressed the Drosophila homolog, rop, in third instar larvae and measured the electrophysiological consequences at the neuromuscular junction. A 3- to 5-fold induction of the rop protein causes a dramatic decrease in neurotransmitter release, suggesting rop may restrict the ability of vesicles to dock or of docked vesicles to fuse. Consistent with this hypothesis, rop overexpression also reduces the number of spontaneous vesicle fusions by more than 50%, and repetitive stimulation results in significant decreases in evoked responses similar to those observed in rab3a mutant mice. However, rop overexpression does not alter significantly the Ca2+ dependence of neurotransmitter release. We propose that the Drosophila n-Sec1/Munc-18 homolog plays a negative role in neurotransmitter release in vivo, in addition to its previously identified positive function, possibly by modulation of docking of synaptic vesicles or activation of a pre-fusion complex at the active zone.

UI MeSH Term Description Entries
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009469 Neuromuscular Junction The synapse between a neuron and a muscle. Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004331 Drosophila melanogaster A species of fruit fly frequently used in genetics because of the large size of its chromosomes. D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018377 Neurotransmitter Agents Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function. Nerve Transmitter Substance,Neurohormone,Neurohumor,Neurotransmitter Agent,Nerve Transmitter Substances,Neurohormones,Neurohumors,Neuromodulator,Neuromodulators,Neuroregulator,Neuroregulators,Neurotransmitter,Neurotransmitters,Substances, Nerve Transmitter,Transmitter Substances, Nerve,Substance, Nerve Transmitter,Transmitter Substance, Nerve
D029721 Drosophila Proteins Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development. Drosophila melanogaster Proteins,Proteins, Drosophila,Proteins, Drosophila melanogaster,melanogaster Proteins, Drosophila
D030801 Animals, Genetically Modified ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring. Animals, Transgenic,Genetically Modified Animals,Transgenic Animals,Founder Animals, Transgenic,GMO Animals,Genetically Engineered Animals,Animal, GMO,Animal, Genetically Engineered,Animal, Genetically Modified,Animal, Transgenic,Animal, Transgenic Founder,Animals, GMO,Animals, Genetically Engineered,Animals, Transgenic Founder,Engineered Animal, Genetically,Engineered Animals, Genetically,Founder Animal, Transgenic,GMO Animal,Genetically Engineered Animal,Genetically Modified Animal,Modified Animal, Genetically,Modified Animals, Genetically,Transgenic Animal,Transgenic Founder Animal,Transgenic Founder Animals

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