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Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes

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dc.contributor.advisor Scarlata, Suzanne en_US
dc.contributor.author Yerramilli, Venkata Siddartha Krishna en_US
dc.contributor.other Department of Physiology and Biophysics. en_US
dc.date.accessioned 2017-09-20T16:51:06Z
dc.date.available 2017-09-20T16:51:06Z
dc.date.issued 2015-05-01 en_US
dc.identifier.uri http://hdl.handle.net/11401/76748 en_US
dc.description 146 pg. en_US
dc.description.abstract γ-Synuclein is a protein of neuronal origin that is highly expressed in late-stage human breast cancers, but not in early-stage breast cancers or non-cancerous breast tissues. In model systems, γ-synuclein binds strongly to phospholipase Cβ2 (PLCβ2). PLCβ2 is activated by heterotrimeric G protein subunits Gαq and Gβγ, and by the small GTPase Rac to generate intracellular calcium signals. PLCβ2 is also highly expressed in breast cancer. In-vitro studies have shown that γ-synuclein binds to the same region of PLCβ2 as Gαq. The work presented in this dissertation reveals a strong binding between γ-synuclein and PLCβ2 in the breast cancer cell line MDA MB 231. In these cells, it was also seen that down-regulation of γ-synuclein reduces the protein level of PLCβ2 while increasing its transcription. γ-Synuclein down-regulation also promotes the interaction between Gαq and PLCβ2 increasing the calcium response to Gαq agonists. γ-Synuclein down-regulation also affects the binding between PLCβ2 and Rac. This change in association impacts Rac-mediated cell migration as demonstrated by decreased cell migration and invasion and changes in cell morphology. This dissertation studies the interaction between γ-synuclein, PLCβ2 and PLCβ2’s binding partners for the first time in cells. This dissertation corroborates recent evidence that shows that γ-synuclein promotes breast cancer cell migration, invasion and proliferation. The dissertation shows for the first time that these effects are partially mediated by γ-synuclein - PLCβ2 interactions. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biophysics en_US
dc.title Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Rebecchi, Mario en_US
dc.contributor.committeemember Cao, Jian en_US
dc.contributor.committeemember El-Maghrabi, Raafat en_US
dc.contributor.committeemember Miller, Todd. en_US

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