Molecular mechanism of fascin function in filopodial formation

Shengyu Yang, Fang Ke Huang, Jianyun Huang, Shuai Chen, Jean Jakoncic, Alejandra Leo-Macias, Ruben Diaz-Avalos, Lin Chen, J. Jillian Zhang, Xin Yun Huang

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Abstract

Filopodia are cell surface protrusions that are essential for cell migration. This finger-like structure is supported by rigid tightly bundled actin filaments. The protein responsible for actin bundling in filopodia is fascin. However, the mechanism by which fascin functions in filopodial formation is not clear. Here we provide biochemical, cryo-electron tomographic, and x-ray crystal structural data demonstrating the unique structural characteristics of fascin. Systematic mutagenesis studies on 100 mutants of fascin indicate that there are two major actin-binding sites on fascin. Crystal structures of four fascin mutants reveal concerted conformational changes in fascin from inactive to active states in the process of actin bundling. Mutations in any one of the actin-binding sites impair the cellular function of fascin in filopodial formation. Altogether, our data reveal the molecular mechanism of fascin function in filopodial formation.

Original languageEnglish (US)
Pages (from-to)274-284
Number of pages11
JournalJournal of Biological Chemistry
Volume288
Issue number1
DOIs
Publication statusPublished - Jan 4 2013

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Yang, S., Huang, F. K., Huang, J., Chen, S., Jakoncic, J., Leo-Macias, A., ... Huang, X. Y. (2013). Molecular mechanism of fascin function in filopodial formation. Journal of Biological Chemistry, 288(1), 274-284. https://doi.org/10.1074/jbc.M112.427971