Current Search: Godenschwege, Tanja A. (x)
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- Title
- Use of Drosophila melanogaster larvae to evaluate cardioactive peptides.
- Creator
- Alishaev, Zahava, Godenschwege, Tanja A., Mari, Frank
- Abstract/Description
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Conopeptides are found in the venom of marine cone snails, aiding in the paralysis of their prey, and have been shown to have potential therapeutic uses in humans. Conopressins are conopeptides that target vasopressin/oxytocin receptors in vascular smooth muscle cells that are found within blood vessels. The crustacean cardioactive peptide (CCAP) is a homologous peptide found in crustaceans and has been shown to behave as a cardioaccelerator in a homologous system. This study describes the...
Show moreConopeptides are found in the venom of marine cone snails, aiding in the paralysis of their prey, and have been shown to have potential therapeutic uses in humans. Conopressins are conopeptides that target vasopressin/oxytocin receptors in vascular smooth muscle cells that are found within blood vessels. The crustacean cardioactive peptide (CCAP) is a homologous peptide found in crustaceans and has been shown to behave as a cardioaccelerator in a homologous system. This study describes the effects of CCAP in Drosophila larvae. We find that CCAP has an inotropic effect by causing a change in the contraction of blood vessels. We further investigate the effects of another possibly cardioactive conopeptide, γ-conopressin-vil, in Drosophila larvae. Elucidating the effects of conopetides in Drosophila larvae may translate to cardioactive therapeutic uses in mammalian systems.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA0005000
- Subject Headings
- College students --Research --United States.
- Format
- Document (PDF)
- Title
- Characterization of Lis-1 loss of function at the neuromuscular junction of Drosophila melangaster larvae.
- Creator
- Vargas, Leticia, Boerner, Jana, Godenschwege, Tanja A.
- Date Issued
- 2013-04-05
- PURL
- http://purl.flvc.org/fcla/dt/3361219
- Subject Headings
- Lissencephaly, Drosophila melanogaster, Mutations
- Format
- Document (PDF)
- Title
- Novel function of PTP69D in giant fiber synapse formation.
- Creator
- Lee, LaTasha Hoskins, Godenschwege, Tanja A., Graduate College
- Abstract/Description
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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 motoneurons 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...
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 motoneurons 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 structurefunction analyses revealed that for GF terminal growth Cat1 function of PTP69D requires the Immunoglobulin and the Cat2 domain, but not the Fibronectin III and the Membrane Proximal Region domains. In contrast, the Fibronectin III, 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 process.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00005831
- Format
- Document (PDF)
- Title
- L1CAM: a potential role in Alzheimer pathology.
- Creator
- Qureshi, Aater, Godenschwege, Tanja A., Harriet L. Wilkes Honors College
- Abstract/Description
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L1-type cell adhesion molecule (L1-CAM) is a synaptic membrane protein that is associated with L1 syndrome, which exhibits spasticity, intellectual disability and hydrocephalus Neuroglian (Nrg) is the invertebrate homologue of L1-CAM in Drosophila melanogaster. In vitro studies have shown L1-CAM is proteolytically cleaved and the intracellular domain (ICD) translocates to the nucleus. There it is involved in the upregulation of genes that are involved in DNA damage response, cell cycle...
Show moreL1-type cell adhesion molecule (L1-CAM) is a synaptic membrane protein that is associated with L1 syndrome, which exhibits spasticity, intellectual disability and hydrocephalus Neuroglian (Nrg) is the invertebrate homologue of L1-CAM in Drosophila melanogaster. In vitro studies have shown L1-CAM is proteolytically cleaved and the intracellular domain (ICD) translocates to the nucleus. There it is involved in the upregulation of genes that are involved in DNA damage response, cell cycle progression, apoptosis and cellular differentiation. In some forms of Alzheimer’s Disease (AD) proteolytic cleavage of L1-CAM are enhanced. We studied the effects of expression of NrgICD in vivo. Our results indicate that ubiquitous expression of NrgICD like its vertebrate homologue resulted in upregulation of NBS1 and c-myc in Drosophila. We found that the ubiquitous expression of NrgICD resulted in reduced viability in various models of oxidative stress. This suggests that enhanced proteolytic cleavage of Nrg/L1-CAM contributes to the pathology of AD. Our results may provide new insights into the cellular mechanisms of neurodegenerative diseases.
Show less - Date Issued
- 2016
- PURL
- http://purl.flvc.org/fau/fd/FA00003688
- Format
- Document (PDF)
- Title
- New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster.
- Creator
- Mejia, Monica, Heghinian, Mari D., Mari, Frank, Godenschwege, Tanja A., McCabe, Brian D.
- Abstract/Description
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Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The a7 subtype of nAChRs is involved in neurological pathologies such as Parkinson’s disease, Alzheimer’s disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster a7 (Da7) has the closest sequence homology to the vertebrate a7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Da7 subunits are essential for the function of the Giant Fiber...
Show moreNicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The a7 subtype of nAChRs is involved in neurological pathologies such as Parkinson’s disease, Alzheimer’s disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster a7 (Da7) has the closest sequence homology to the vertebrate a7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Da7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Da7 nAChR’s ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Da7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Da7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Da7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Da7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Da7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Da7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling.
Show less - Date Issued
- 2013-05-30
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000083
- Format
- Citation
- Title
- Differential Effects of Human L1CAM Mutations on Complementing Guidance and Synaptic Defects in Drosophila melanogaster.
- Creator
- Kudumala, Sirisha, Freund, Julie, Hortsch, Michael, Godenschwege, Tanja A., Labrador, Juan-Pablo
- Abstract/Description
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A large number of different pathological L1CAM mutations have been identified that result in a broad spectrum of neurological and non-neurological phenotypes. While many of these mutations have been characterized for their effects on homophilic and heterophilic interactions, as well as expression levels in vitro, there are only few studies on their biological consequences in vivo. The single L1-type CAM gene in Drosophila, neuroglian (nrg), has distinct functions during axon guidance and...
Show moreA large number of different pathological L1CAM mutations have been identified that result in a broad spectrum of neurological and non-neurological phenotypes. While many of these mutations have been characterized for their effects on homophilic and heterophilic interactions, as well as expression levels in vitro, there are only few studies on their biological consequences in vivo. The single L1-type CAM gene in Drosophila, neuroglian (nrg), has distinct functions during axon guidance and synapse formation and the phenotypes of nrg mutants can be rescued by the expression of human L1CAM. We previously showed that the highly conserved intracellular FIGQY Ankyrin-binding motif is required for L1CAM-mediated synapse formation, but not for neurite outgrowth or axon guidance of the Drosophila giant fiber (GF) neuron. Here, we use the GF as a model neuron to characterize the pathogenic L120V, Y1070C, C264Y, H210Q, E309K and R184Q extracellular L1CAM missense mutations and a L1CAM protein with a disrupted ezrin–moesin–radixin (ERM) binding site to investigate the signaling requirements for neuronal development. We report that different L1CAM mutations have distinct effects on axon guidance and synapse formation. Furthermore, L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila. In addition, the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation. Thus, the pathological phenotypes observed in humans are likely to be caused by the disruption of signaling required for both, guidance and synaptogenesis.
Show less - Date Issued
- 2013-10-14
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000080
- Format
- Citation
- Title
- Expression of human amyloid precursor protein in the skeletal muscles of Drosophila results in age- and activity-dependent muscle weakenss.
- Creator
- Kim, Chul, Srivastava, Sapeckshita, Rice, Marian, Godenschwege, Tanja A., Bentley, Brooke, Ravi, Saranya, Shao, Shuang, Woodard, Craig T., Schwartz, Lawrence M.
- Date Issued
- 2011-04-25
- PURL
- http://purl.flvc.org/fcla/dt/3327608
- Format
- Document (PDF)
- Title
- Transsynaptic Coordination of Synaptic Growth, Function, and Stability by the L1-Type CAM Neuroglian.
- Creator
- Enneking, Eva-Maria, Kudumala, Sirisha R., Moreno, Eliza, Stephan, Raiko, Boerner, Jana, Godenschwege, Tanja A., Pielage, Jan, Bellen, Hugo J.
- Date Issued
- 2013-04-16
- PURL
- http://purl.flvc.org/fau/fd/FAUIR000106
- Format
- Citation
- Title
- A Novel Role of the Ankyrin-Binding Motif of L1-Type CAM Neuroglian in Nuclear Import and Transcriptional Regulation of Myc.
- Creator
- Kakad, Priyanka P., Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
L1-type cell adhesion molecule (L1CAM) plays an essential role in the development of nervous system and is also highly relevant for the progression of diseases such as Alzheimer’s disease, stroke and cancers, some of the leading causes of human mortality. In addition to its canonical role as a plasma membrane protein organizing the cytoskeleton, recent in vitro studies have revealed that transmembrane as well as cytosolic fragments of proteolytically cleaved vertebrate L1CAM translocate to...
Show moreL1-type cell adhesion molecule (L1CAM) plays an essential role in the development of nervous system and is also highly relevant for the progression of diseases such as Alzheimer’s disease, stroke and cancers, some of the leading causes of human mortality. In addition to its canonical role as a plasma membrane protein organizing the cytoskeleton, recent in vitro studies have revealed that transmembrane as well as cytosolic fragments of proteolytically cleaved vertebrate L1CAM translocate to the nucleus and regulate expression of genes involved in DNA post-replication repair, cell cycle control, migration and differentiation. However, little is known about the in vivo function of L1CAM in the adult nervous system. This dissertation research focuses on studying in vivo nuclear translocation and function of L1CAM. Using the Drosophila model system, we first show that the sole Drosophila L1CAM homolog, Neuroglian (Nrg), is proteolytically cleaved by Alzheimer’s associated secretases, similar to L1CAM, and is also translocated to the nucleus in the adult nervous system. Subsequently, we have shown that the deletion of highly conserved Ankyrin binding domain or FIGQY motif disrupts nuclear import. Further experiments have revealed that the nuclear translocation of Nrg is in fact regulated by the phosphorylation of the FIGQY motif. Importantly, our studies also show transgenic expression of full-length Nrg or the intracellular domain of Nrg resulted in increased myc expression, which is associated with increased sensitivity to oxidative stress and reduced life span. On the other hand, deletion of the FIGQY motif or mutations preventing its phosphorylation led to decrease in myc expression. In summary, we have identified a novel role for the highly conserved Ankyrin binding domain in nuclear translocation and transcriptional regulation of the Drosophila myc oncogene, which is of high relevance to neurodegenerative diseases and cancer associated with oxidative stress.
Show less - Date Issued
- 2018
- PURL
- http://purl.flvc.org/fau/fd/FA00013076
- Subject Headings
- Cell adhesion molecules., Myc proteins., Transcription, Genetic., Transcription factors, Gene expression., Ankyrins., Translocation, Genetic.
- Format
- Document (PDF)
- 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.
Show less - 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)
- Title
- Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster.
- Creator
- Kudumala, Sirisha, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
- Abstract/Description
-
Neuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic...
Show moreNeuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic connectivity to control the development and maintenance of synaptic connections within neuronal circuits. Here we characterized the essential role of nrg in regulating synaptic structure and function in vivo in a well characterized Drosophila central synapse model neuron, the Giant Fiber (GF) system. Previous studies from our lab revealed that the phosphorylation status of the tyrosine in the Ankyrin binding FIGQY motif in the intracellular domain of Nrg iscrucial for synapse formation of the GF to Tergo-Trochanteral Motor neuron (TTMn) synapse in the GF circuit. The present work provided us with novel insights into the role of Nrg-Ank interaction in regulating Nrg function during synapse formation and maintenance. By utilizing a sophisticated Pacman based genomic rescue strategy we have shown that dynamic regulation of the Neuroglian–Ankyrin interaction is required to coordinate transsynaptic development in the GF–TTMn synapse. In contrast, the strength of Ankyrin binding directly controls the balance between synapse formation and maintenance at the NMJ. Human L1 pathological mutations affect different biological processes distinctively and thus their proper characterization in vivo is essential to understand L1CAM function. By utilizing nrg14;P[nrg180ΔFIGQY] mutants that have exclusive synaptic defects and the previously characterized nrg849 allele that affected both GF guidance and synaptic function, we were able to analyze pathological L1CAM missense mutations with respect to their effects on guidance and synapse formation in vivo. We found that the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation and not for axon guidance while L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila.
Show less - Date Issued
- 2014
- PURL
- http://purl.flvc.org/fau/fd/FA00004131, http://purl.flvc.org/fau/fd/FA00004131
- Subject Headings
- Cell adhesion molecules, Cellular signal transduction, Cognitive neuroscience, Cognitive neuroscience, Drosophila melanogaster, Molecular neurobiology
- Format
- Document (PDF)