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Highwire's characterization and signaling roles in Drosophila central synapse formation
Title
Highwire's characterization and signaling roles in Drosophila central synapse formation.
Creator
Rowland, Kimberly Diane., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
The assembly and maintenance of central synapses is a complex process, requiring myriad genes and their products. Highwire is a large gene containing a RING domain, characteristic of ubiquitin E3 ligases. Highwire has been shown to restrain axon growth and control synaptogenesis at a peripheral synapse. Here I examine the roles of Highwire at a central synapse in the adult Drosophila Giant Fiber System (GFS). Highwire is indeed necessary for proper axonal growth as well as synaptic...
Show moreThe assembly and maintenance of central synapses is a complex process, requiring myriad genes and their products. Highwire is a large gene containing a RING domain, characteristic of ubiquitin E3 ligases. Highwire has been shown to restrain axon growth and control synaptogenesis at a peripheral synapse. Here I examine the roles of Highwire at a central synapse in the adult Drosophila Giant Fiber System (GFS). Highwire is indeed necessary for proper axonal growth as well as synaptic transmission in the GFS. Differences arise between the central synapse and the neuromuscular junction (NMJ), where highwire was initially characterized : expresion from the postsynaptic cell can rescue highwire synaptic defects, which is not seen at the NMJ. In addition, a MAP kinase signaling pathway regulated by highwire at the NMJ has differing roles at a central synapse. Wallenda MAPK can rescue not only the highwire anatomical phenotype but also the defects seen in transmission. Another distinction is seen here : loss of function basket and Dfos enhance the highwire anatomical phenotype while expression of dominant negative basket and Dfos suppress the highwire phenotype. As a result we have compared the signaling pathway in flies and worms and found that the NMJ in the two organisms use a parallel pathway while the central synapse uses a distinct pathway.
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Date Issued
2012
PURL
http://purl.flvc.org/FAU/3352826
Subject Headings
Cellular control mechanisms, Cellular signal transduction, Cell differentiation, Gene expression, Genetic transcription, Transcription factors, Drosophila melanogaster, Cytogenetics
Format
Document (PDF)
Methionine sulfoxide reductase (MSR) modulates lifespan andLocomotion in drosophila melanogaster
Title
Methionine sulfoxide reductase (MSR) modulates lifespan andLocomotion in drosophila melanogaster.
Creator
Bruce, Lindsay, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Oxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in...
Show moreOxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in proteins back to methionine. This study, using Drosophila melanogaster, decribes the first animal system lacking both MsrA and MsrB. The loss of either MsrA or MsrB had no effect on lifespan in Drosophila, but loss of MsrB results in a slight decrease in locomotor activity from middle age onward. Double mutants lacking both forms of Msr have a significantly decreased lifespan and decreased locomotor activity at all ages examined. The double Msr mutants had no detectable increase in protein oxidation or decrease in mitochondrial function and were not more sensitive to oxidative stress. These results suggested that other cellular antioxidant systems were protecting the flies against oxidative damage and the decreased life span observed in the double knockouts was not due to widespread oxidative damage. However, one cannot exclude limited oxidative damage to a specific locus or cell type. In this regard, it was observed that older animals, lacking both MsrA and MsrB, have significantly reduced levels of dopamine, suggesting there might be oxidative damage to the dopaminergic neurons. Preliminary results also suggest that the ratio of F to G actin is skewed towards G actin in all mutants. The present results could have relevance to the loss of dopaminergic neurons in Parkinson’s disease.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004431, http://purl.flvc.org/fau/fd/FA00004431
Subject Headings
Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress, Proteins -- Chemical modification
Format
Document (PDF)
Characterization of receptor protein tyrosine phosphatase PTP69D in the giant fiber circuit
Title
Characterization of receptor protein tyrosine phosphatase PTP69D in the giant fiber circuit.
Creator
Lee, LaTasha Hoskins, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
PTP69D is a receptor protein tyrosine phosphatase (RPTP) with two intracellular catalytic domains (Cat1 and Cat2), which has been shown to play a role in axon outgrowth and guidance of embryonic motorneurons, as well as targeting of photoreceptor neurons in the visual system of Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant fiber (GF) neurons; two interneurons in the central nervous system (CNS) that control the escape response of the fly. In...
Show morePTP69D is a receptor protein tyrosine phosphatase (RPTP) with two intracellular catalytic domains (Cat1 and Cat2), which has been shown to play a role in axon outgrowth and guidance of embryonic motorneurons, as well as targeting of photoreceptor neurons in the visual system of Drosophila melanogaster. Here, we characterized the developmental role of PTP69D in the giant fiber (GF) neurons; two interneurons in the central nervous system (CNS) that control the escape response of the fly. In addition to guidance and targeting functions, our studies reveal an additional role for PTP69D in synaptic terminal growth in the CNS. We found that inhibition of phosphatase activity in catalytic domain (Cat1) proximal to the transmembrane domain did not affect axon guidance or targeting but resulted in stunted terminal growth of the GFs. Cell autonomous rescue and knockdown experiments demonstrated a function for PTP69D in the GFs, but not its postsynaptic target neurons. In addition,complementation studies and structure-function analyses revealed that for GF terminal growth, Cat1 function of PTP69D requires the immunoglobulin and the Cat2 domain but not the fibronectin type III repeats nor the membrane proximal region. In contrast, the fibronectin type III repeats, but not the immunoglobulin domains, were previously shown to be essential for axon targeting of photoreceptor neurons. Thus, our studies uncover a novel role for PTP69D in synaptic terminal growth in the CNS that is mechanistically distinct from its function during earlier developmental processes.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00004301, http://purl.flvc.org/fau/fd/FA00004301
Subject Headings
Drosophila melanogaster., Protein-tyrosine phosphatase--Metabolism., Protein-tyrosine kinase., Protein kinases--Inhibitors., Phosphoprotein phosphatases., Transcription factors., Cell receptors., Cellular signal transduction.
Format
Document (PDF)
Phenotypic and behavioral effects of methionine sulfoxide reductase deficiency and oxidative stress in Drosophila melanogaster
Title
Phenotypic and behavioral effects of methionine sulfoxide reductase deficiency and oxidative stress in Drosophila melanogaster.
Creator
Mulholland, Kori., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Harman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of...
Show moreHarman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of this study was to investigate how the absence of one or both forms of Msr affects locomotion in Drosophila using both traditional genetic mutants and more recently developed RNA interference (RNAi) strains. Results indicate that lack of MsrA does not affect locomotion. However, lack of MsrB drastically reduces rates of locomotion in all age classes. Furthermore, creation of an RNAi line capable of knocking down both MsrA and MsrB in progeny was completed.
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Date Issued
2013
PURL
http://purl.flvc.org/fcla/dt/3362558
Subject Headings
Drosophila melanogaster, Genetics, Aging, Molecular aspects, Oxidative stress, Mitochondrial pathology, Cellular signal transduction, Oxidation-reduction reaction, Biochemical markers, Mutation (Biology)
Format
Document (PDF)
Reduced Reproductivity and Larval Locomotion in the Absence of Methionine Sulfoxide Reductase in Drosophila
Title
Reduced Reproductivity and Larval Locomotion in the Absence of Methionine Sulfoxide Reductase in Drosophila.
Creator
Singkornrat, Diana, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
The inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that...
Show moreThe inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that these animals exhibit a 20 hour delay in development of the third instar larvae (unpublished data). My studies have further shown that the prolonged third-instar stage is due to a reduced growth rate associated with slower food intake and a markedly slower motility. These Msr-deficient animals also exhibit decreased egg-laying that can be attributed to a lack of female receptivity to mating.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004777, http://purl.flvc.org/fau/fd/FA00004777
Subject Headings
Proteins--Chemical modification., Oxidative stress., Oxidation-reduction reaction., Drosophila melanogaster--Genetics., Mitochondrial pathology., Cellular signal transduction., Mutation (Biology), Aging--Molecular aspects.
Format
Document (PDF)

Pages