Synaptic plasticity, in its broadest sense, can be defined as the ability of synapses to be modified structurally and functionally in response to various internal and external factors. Growing evidence has established that at the very core of these modifications are alterations in the cytoskeletal architecture. This discovery has led to the unearthing of a number of signaling pathways that might be involved in cytoskeletal regulation and also in the regulation of other aspects of synapse development and plasticity. In this regard, polarity proteins and secreted morphogens such as the Wnt proteins, typically involved in embryonic development, are emerging as critical determinants of synaptic growth and plasticity. However, their mechanism of action at synapses needs further investigation. Additionally, not much is known about how these morphogens are secreted or transported across synapses. Using the Drosophila larval NMJ as a model system, I have addressed aspects related to the issues mentioned above in the subsequent body of work. In the first half of my thesis, I have uncovered a role for the aPKC/Baz/Par-6 polarity protein complex in the regulation of the postsynaptic actin cytoskeleton in conjunction with the lipid and protein phosphatase PTEN. In the second half of my thesis, I have contributed to the elucidation of mechanisms underlying the secretion of Wg, the Drosophila Wnt homolog. Our findings suggest that Wnts might be secreted via a previously unidentified mechanism involving the release of exosome like vesicles from the presynapse and this process requires Evi/Wntless (Evi), a protein dedicated to Wnt secretion. Alterations in signaling pathways and aberrant cytoskeletal regulation lead to a variety of neurological disorders. The body of work in this thesis will provide a deeper understanding of the mechanisms involved in synaptic plasticity and provide a basis for uncovering similar pathways in the context of vertebrate synapses.
| Identifer | oai:union.ndltd.org:umassmed.edu/oai:escholarship.umassmed.edu:gsbs_diss-1443 |
| Date | 10 August 2009 |
| Creators | Ramachandran, Preethi |
| Publisher | eScholarship@UMassChan |
| Source Sets | University of Massachusetts Medical School |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Morningside Graduate School of Biomedical Sciences Dissertations and Theses |
| Rights | Copyright is held by the author, with all rights reserved., select |
Page generated in 0.0027 seconds