title: The Breast Cancer Susceptibility Gene Product (γ-Synuclein) Alters Cell Behavior through its [corrected] Interaction with Phospholipase Cβ.
abstract: The breast cancer susceptibility gene protein, also known as γ-synuclein, is highly expressed in human breast cancer in a stage-specific manner, with highest expression in late stage cancer. In model systems, γ-synuclein binds phospholipase Cβ2 which is regulated by Gαq to generate intracellular Ca(2+) signals. PLCβ2, which is also absent in normal tissue but highly expressed in breast cancer, is additionally regulated by Rac to promote migration pathways. We have found that γ-synuclein binds to the same region of PLCβ2 as Gαq. Using cells that mimic stage 4 breast cancer (MDA MB 231), we show that down-regulation of γ-synuclein reduces the protein level of PLCβ but increases the transcript level over 40 fold. γ-Synuclein down-regulation also promotes the interaction between Gαq and PLCβ resulting in a stronger Ca(2+) response to Gαq agonists. The ability of γ-synuclein to interfere with Gαq-PLCβ interactions allows more PLCβ to colocalize with Rac impacting Rac-mediated pathways that may give rise to cancerous phenotypes.
authors.affiliation: Dept of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, 11794-8661, United States.
authors.forename: V Siddartha
authors.initials: VS
authors.lastname: Yerramilli
authors.affiliation: Dept of Physiology & Biophysics, Stony Brook University, Stony Brook, NY, 11794-8661, United States; Dept. of Chemistry and Biochemistry, Worcester Polytechnic Institute, Worcester, MA, 01609, United States. Electronic address: sfscarlata@wpi.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Scarlata
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism*; D051845:gamma-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D015513:Oncogene Proteins; D051845:gamma-Synuclein; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins
keywords: Calcium signaling; Cell migration; Cell morphology; Phospholipase Cβ2; γ-Synuclein