Role of gamma-synuclein in microtubule regulation

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• 作者：Hong Zhang^a ; Ange Kouadio^b ; Donna Cartledge^c ; Andrew K. Godwin^d ; ^{AGodwin@KUMC.edu"" rel=""nofollow}
• 关键词：Gamma-synuclein ; Cancer ; Drug resistance ; Paclitaxel ; Microtubule
• 刊名：Experimental Cell Research
• 出版年：2011
• 出版时间：10 June 2011
• 年：2011
• 卷：317
• 期：10
• 页码：1330-1339
• 全文大小：1153 K

文摘

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.