Role of gamma-synuclein in microtubule regulation.

Abstract

Gamma-synuclein is a neuronal protein found in peripheral and motor nerve systems. It becomes highly expressed in metastatic but not in primary tumor or normal tissues. The close association between gamma-synuclein expression and cancer spreading has been demonstrated in a broad range of malignancies. Our previous study showed that exogenous expression of gamma-synuclein in ovarian and breast cancer cells significantly enhanced cell migration and resistance to paclitaxel-induced apoptotic death. In our current research, we found that gamma-synuclein can affect microtubule properties and act as a functional microtubule associated protein. In vitro assays revealed that gamma-synuclein can bind and promote tubulin polymerization, induce the microtubule bundling and alter microtubule morphology developed in the presence of microtubule associated protein 2 (MAP2). Using cancer cell lysate, gamma-synuclein protein was found to be localized in both cytosolic compartment and extracted cytoskeleton portion. Immunofluorescence staining demonstrated that gamma-synuclein can colocalize with microtubule in HeLa cells and decrease rigidity of microtubule bundles caused by paclitaxel. In human ovarian cancer epithelial A2780 cells, gamma-synuclein overexpression improved cell adhesion and microtubule structure upon paclitaxel treatment. Importantly, it led to microtubule-dependent mitochondria clustering at perinuclear area. These observations suggest that overexpression of gamma-synuclein may reduce cell chemo-sensitivity of tumor cells through decreasing microtubule rigidity. In summary, our studies suggested that gamma-synuclein can directly participate in microtubule regulation.

• Authors: Hong Zhang, Ange Kouadio, Donna Cartledge, Andrew K Godwin
• Journal: Experimental cell research (Exp Cell Res) Vol. 317 Issue 10 Pg. 1330-9 (Jun 10 2011) ISSN: 1090-2422 [Electronic] United States
• PMID: 20974125 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• MAP2 protein, human
• Microtubule-Associated Proteins
• Tubulin
• gamma-Synuclein
• Paclitaxel

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Breast Neoplasms (metabolism, pathology)
• Carcinoma, Ovarian Epithelial
• Cytoskeleton (drug effects, metabolism)
• Female
• Fluorescent Antibody Technique
• Humans
• Microtubule-Associated Proteins (metabolism)
• Microtubules (drug effects, metabolism)
• Neoplasms, Glandular and Epithelial (metabolism, pathology)
• Ovarian Neoplasms (metabolism, pathology)
• Paclitaxel (pharmacology)
• Tubulin (metabolism)
• Tumor Cells, Cultured
• gamma-Synuclein (metabolism)