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Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster
| Title: | Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster. |
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| Name(s): |
Kudumala, Sirisha, author Godenschwege, Tanja A., Thesis advisor Florida Atlantic University, Degree grantor Charles E. Schmidt College of Science Department of Biological Sciences |
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| Type of Resource: | text | |
| Genre: | Electronic Thesis Or Dissertation | |
| Date Created: | 2014 | |
| Date Issued: | 2014 | |
| Publisher: | Florida Atlantic University | |
| Place of Publication: | Boca Raton, Fla. | |
| Physical Form: | application/pdf | |
| Extent: | 205 p. | |
| Language(s): | English | |
| Summary: | 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 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. | |
| Identifier: | FA00004131 (IID) | |
| Degree granted: | Dissertation (Ph.D.)--Florida Atlantic University, 2014. | |
| Collection: | FAU Electronic Theses and Dissertations Collection | |
| Note(s): | Includes bibliography. | |
| Subject(s): |
Cell adhesion molecules Cellular signal transduction Cognitive neuroscience Cognitive neuroscience Drosophila melanogaster Molecular neurobiology |
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| Held by: | Florida Atlantic University Libraries | |
| Sublocation: | Digital Library | |
| Links: | http://purl.flvc.org/fau/fd/FA00004131 | |
| Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00004131 | |
| Use and Reproduction: | Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder. | |
| Use and Reproduction: | http://rightsstatements.org/vocab/InC/1.0/ | |
| Host Institution: | FAU | |
| Is Part of Series: | Florida Atlantic University Digital Library Collections. |
