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The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein

Cellular and Molecular Life Sciences volume 68, pages 1633–1643 (2011)Cite this article

Abstract

The neuronal Cdk5 activator p35 is involved in a multitude of neuronal activities, including cytoskeletal organization. We show here that p35 directly interacts with filamentous actin (F-actin) but not with monomeric actin (G-actin). Through binding, p35 induces the formation of actin bundles and stabilizes F-actin against dilution-induced depolymerization. p35 forms intermolecular self-associations, suggesting that p35 cross-links actin filaments into bundles via its intermolecular self-association. p35 dimerization and association with F-actin occur at the N-terminal region that is absent in the calpain-cleaved product p25, indicating that such p35 properties are lost by its truncation induced under neurotoxic conditions. Using p35 phosphorylated by Cdk5 and a mutational approach, we demonstrate that the phosphorylation of p35 promotes its homodimerization and p35-induced formation of F-actin bundles. In addition, the phosphorylation regulates p35 distribution to microtubule and actin cytoskeletons. Together, these observations define a novel function for p35 in cytoskeletal regulation.

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Acknowledgments

We thank Dr. Henry N. Higgs (Dartmouth Medical School) for advice on actin polymerization assays. This work was supported by the Research Grants Council (General Research Fund and Collaborative Research Fund) and the University Grants Committee (Area of Excellence Scheme and Special Equipment Grant) of Hong Kong.

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Affiliations

  1. Department of Biochemistry, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Lisheng He, Zhaojun Zhang, Yan Yu & Robert Z. Qi

  2. Institute of Medical Biology, 8A Biomedical Grove, #06-06, Immunos, Singapore, 138648, Republic of Singapore

    Sohail Ahmed

  3. Menzies Research Institute, University of Tasmania, Hobart, TAS, Australia

    Nam Sang Cheung

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  1. Lisheng He
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  2. Zhaojun Zhang
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  3. Yan Yu
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  4. Sohail Ahmed
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  6. Robert Z. Qi
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Correspondence to Robert Z. Qi.

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L. He and Z. Zhang contributed equally to this work.

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He, L., Zhang, Z., Yu, Y. et al. The neuronal p35 activator of Cdk5 is a novel F-actin binding and bundling protein. Cell. Mol. Life Sci. 68, 1633–1643 (2011). https://doi.org/10.1007/s00018-010-0562-9

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  • DOI: https://doi.org/10.1007/s00018-010-0562-9

Keywords

  • Cdk5
  • Cdk5 activator
  • Actin
  • Actin-binding proteins
  • Protein phosphorylation