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SSeCKS promoted lipopolysaccharide-sensitized astrocytes migration via increasing β-1,4-galactosyltransferase-I activity

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Abstract

Astrocytes migration is essential in the formation of the glial scar during the injury response process of the central nervous system (CNS) especially during inflammation. Integrin β1 is part of the extracellular matrix receptors in the CNS and it has been reported that integrin β-deficient astrocytes randomly migrate into wounds. Previous studies have found that β-1,4 Galactosyltransferase-I (β-1,4-GalT-I) enhanced the β-1,4-galactosylation of integrin β1. Src-suppressed C kinase substrate (SSeCKS) is an inflammatory response protein which functionally interacts with β-1,4 Galactosyltransferase-I (β-1,4-GalT-I). In this study we aim to investigate the role of SSeCKS and β-1,4-GalT-I in the migration of astrocytes during lipopolysaccharide (LPS)-induced inflammation. Coimmunoprecipitation and immunofluorescence assays have demonstrated that SSeCKS and β-1,4-GalT-I were significantly enhanced in LPS-treated astrocytes and their interactions may occur in the Trans-Golgi Network. Lectin blot showed that the knockdown of β-1,4-GalT-I could inhibit the β-1,4-galactosylation of glycoproteins including integrin β1 with and without LPS, and that SSeCKS knockdown inhibits the β-1,4-galactosylation of glycoproteins including integrin β1 only in LPS-induced astrocytes. Additionally, wound healing assays indicated that β-1,4-GalT-I knockdown could inhibit astrocytes migration with and without LPS but SSeCKS inhibited cell migration only when LPS was present. Therefore our findings suggest that SSeCKS affects astrocytes migration by regulating the β-1,4-galactosylation of glycoproteins including integrin β1, via β-1,4-GalT-I expression in LPS-sensitized astrocytes.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 31600402), China Postdoctoral Science Fund (Grant No. 2017M621895), Zhejiang Province Postdoctoral Research Fund (Grant No. ZX2016000849), Ningbo Postdoctoral Research Fund (Grant No. ZX2017000053), Natural Science Foundation of Ningbo (Grant No. 2017A610216, 2016A610205), Natural Science Foundation of Zhejiang Province (Grant No. Y16H070001), Research Project of Zhejiang Provincial Department of Education (Y201738586), Agricultural Project of Public Welfare Technology Research in Zhejiang Provincial Science and Technology Department (Grant No. ZX2014C32047).

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Authors and Affiliations

  1. Ningbo College of Health Sciences, Ningbo, 315211, Zhejiang, People’s Republic of China

    Hua Wei, Lingli Jiang, Ning Sun, Qingzhi Ling, Shaohua Ma, Lingli Zhang & Tao Tao

  2. Ningbo University, Ningbo, 315211, Zhejiang, People’s Republic of China

    Hua Wei, Leiting Xu, Lianliang Liu, Derry Minyao Ng, Maria Haleem, Qinwen Wang & Tao Tao

  3. Medical School of Nantong University, Nantong, 226001, Jiangsu, People’s Republic of China

    Chunmiao Li

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  1. Hua Wei
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Wei, H., Xu, L., Li, C. et al. SSeCKS promoted lipopolysaccharide-sensitized astrocytes migration via increasing β-1,4-galactosyltransferase-I activity. Neurochem Res 44, 839–848 (2019). https://doi.org/10.1007/s11064-019-02716-5

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