Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes
Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes
| dc.identifier.uri | http://hdl.handle.net/11401/76748 | |
| 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 | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.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. | |
| dcterms.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. | |
| dcterms.available | 2017-09-20T16:51:06Z | |
| dcterms.contributor | Rebecchi, Mario | en_US |
| dcterms.contributor | Scarlata, Suzanne | en_US |
| dcterms.contributor | Cao, Jian | en_US |
| dcterms.contributor | El-Maghrabi, Raafat | en_US |
| dcterms.contributor | Miller, Todd. | en_US |
| dcterms.creator | Yerramilli, Venkata Siddartha Krishna | |
| dcterms.dateAccepted | 2017-09-20T16:51:06Z | |
| dcterms.dateSubmitted | 2017-09-20T16:51:06Z | |
| dcterms.description | Department of Physiology and Biophysics. | en_US |
| dcterms.extent | 146 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76748 | |
| dcterms.issued | 2015-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:51:06Z (GMT). No. of bitstreams: 1 Yerramilli_grad.sunysb_0771E_12626.pdf: 4127855 bytes, checksum: 5b18917f109d13c39fc48f7058190bc8 (MD5) Previous issue date: 2015 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biophysics | |
| dcterms.title | Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes | |
| dcterms.title | Interactions between γ-Synuclein and Phospholipase Cβ and their effects on Cancer Phenotypes | |
| dcterms.type | Dissertation |
