Molecular and Genetic Analysis of Synaptic Signaling in Drosophila

Persistent Link:
http://hdl.handle.net/10150/193514
Title:
Molecular and Genetic Analysis of Synaptic Signaling in Drosophila
Author:
Jackson, Taryn
Issue Date:
2005
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Molecular and genetic analysis of synaptic signaling in Drosophila has yielded many insights into nervous system development, properties of synaptic transmission, and how long-lasting changes in neurons occur. Synaptic signaling components required for synaptic transmission and pathways leading to nervous system plasticity are typically conserved from insects to humans. The role of proteins and genes in synaptic function in flies can be analyzed from the level of a single synapse to complex behaviors in the whole organism. Because of a fully sequenced genome and the ease of mutagenesis in flies, genetic screens have been useful in identifying novel regulators of synaptic transmission and long-term memory.In flies, conditional mutations affecting synaptic transmission at nerve terminals often lead to temperature sensitive paralysis. In a screen for mutations that interact with Drosophila shibirets mutants, the stoned gene was identified as a regulator of synaptic vesicle cycling. Stoned encodes two neuronally expressed proteins, stonedA and B, which are required for synaptic vesicle recycling and normal synaptic transmission. However, the exact functions of the two stoned proteins are not fully understood. We investigate distinct roles of the stoned proteins here and show that stoned has a novel role in synaptic growth.Memory in flies can be divided into genetically distinct phases based on the requirement for protein synthesis and activation of the transcription factor CREB. Novel regulators of long-term olfactory avoidance memory were isolated in a mutant screen in flies. Mutants in the Drosophila gene lk6, homologous to the translational regulator MNK, have defects in long-term olfactory avoidance memory. We find that lk6 is highly expressed in the fly nervous system, and is activated by and functions downstream of Ras/ERK signaling in fly neurons. Insights provided here from Drosophila add to the evidence that MNK may be the link between ERK signaling and the regulation of translation in long-term plasticity.Ultimately, understanding synaptic function has therapeutic potential to aid in alleviation of nervous system dysfunction. Insight into the molecular pathways underlying plasticity and long-term memory gained from studies in flies, mollusks, and rodents has been pivotal in the development of potential drugs to aid in memory deficits in humans.
Type:
text; Electronic Dissertation
Keywords:
drosophila; neuroscience; learning and memory; synaptic plasticity; synaptic signaling
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Neuroscience; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Ramaswami, Mani
Committee Chair:
Ramaswami, Mani

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleMolecular and Genetic Analysis of Synaptic Signaling in Drosophilaen_US
dc.creatorJackson, Tarynen_US
dc.contributor.authorJackson, Tarynen_US
dc.date.issued2005en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractMolecular and genetic analysis of synaptic signaling in Drosophila has yielded many insights into nervous system development, properties of synaptic transmission, and how long-lasting changes in neurons occur. Synaptic signaling components required for synaptic transmission and pathways leading to nervous system plasticity are typically conserved from insects to humans. The role of proteins and genes in synaptic function in flies can be analyzed from the level of a single synapse to complex behaviors in the whole organism. Because of a fully sequenced genome and the ease of mutagenesis in flies, genetic screens have been useful in identifying novel regulators of synaptic transmission and long-term memory.In flies, conditional mutations affecting synaptic transmission at nerve terminals often lead to temperature sensitive paralysis. In a screen for mutations that interact with Drosophila shibirets mutants, the stoned gene was identified as a regulator of synaptic vesicle cycling. Stoned encodes two neuronally expressed proteins, stonedA and B, which are required for synaptic vesicle recycling and normal synaptic transmission. However, the exact functions of the two stoned proteins are not fully understood. We investigate distinct roles of the stoned proteins here and show that stoned has a novel role in synaptic growth.Memory in flies can be divided into genetically distinct phases based on the requirement for protein synthesis and activation of the transcription factor CREB. Novel regulators of long-term olfactory avoidance memory were isolated in a mutant screen in flies. Mutants in the Drosophila gene lk6, homologous to the translational regulator MNK, have defects in long-term olfactory avoidance memory. We find that lk6 is highly expressed in the fly nervous system, and is activated by and functions downstream of Ras/ERK signaling in fly neurons. Insights provided here from Drosophila add to the evidence that MNK may be the link between ERK signaling and the regulation of translation in long-term plasticity.Ultimately, understanding synaptic function has therapeutic potential to aid in alleviation of nervous system dysfunction. Insight into the molecular pathways underlying plasticity and long-term memory gained from studies in flies, mollusks, and rodents has been pivotal in the development of potential drugs to aid in memory deficits in humans.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectdrosophilaen_US
dc.subjectneuroscienceen_US
dc.subjectlearning and memoryen_US
dc.subjectsynaptic plasticityen_US
dc.subjectsynaptic signalingen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineNeuroscienceen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorRamaswami, Manien_US
dc.contributor.chairRamaswami, Manien_US
dc.contributor.committeememberRamaswami, Manien_US
dc.contributor.committeememberNighorn, Alanen_US
dc.contributor.committeememberLevine, Richarden_US
dc.contributor.committeememberGronenberg, Wulfilaen_US
dc.identifier.proquest1356en_US
dc.identifier.oclc137355215en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.