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Phosphorylation-independent membrane relocalization of ezrin following association with Dbl in vivo

Oncogene volume 23, pages 4098–4106 (2004)Cite this article

Abstract

Ezrin, a widespread protein involved in cell migration, morphogenesis and cell adhesion, belongs to a large family of proteins known as ERM (ezrin, radixin, moesin). These three closely related proteins are thought to function as linkers between plasma membrane and actin cytoskeleton and their function is regulated by the small GTP-binding protein Rho. It has been previously shown that the active form of radixin can bind in vitro to Dbl, a Rho-specific guanine nucleotide exchange factor, although an in vivo interaction has not yet been demonstrated. In this paper, we attempted to investigate whether ezrin can also associate with Dbl. We show here that Dbl protein can effectively bind both in vitro and in vivo to the N-terminal region (amino acids 1–531) of a constitutively active mutant of ezrin and with the full-length molecule. We found that this binding is mediated by the Dbl pleckstrin homology domain, responsible for the proper subcellular localization of the Dbl protein. Moreover, we show that Dbl induces localization to the plasma membrane of both the active deletion mutant and the full-length ezrin proteins. Finally, we show that the relocalization of ezrin is independent of Dbl GEF activity. These results indicate that Dbl could induce translocation of ezrin to the plasma membrane through a mechanism that does not require ezrin C-terminus phosphorylation by Rho-associated kinases.

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Acknowledgements

We are grateful to Dr M Arpin for providing pCB6 ezrin. This work was supported by grants from the Italian Association for Cancer Research (AIRC), from Compagnia di S Paolo, Torino and from the Italian Health Ministry.

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Authors and Affiliations

  1. Laboratorio di Biologia Molecolare, Istituto G Gaslini, Largo G Gaslini 5, 16147, Genova, Italy

    Cristina Vanni, Alessia Parodi, Catherine Ottaviano & Alessandra Eva

  2. Dipartimento di Medicina Sperimentale e Patologia, Università di Roma ‘La Sapienza’, Roma, 00161, Italy

    Patrizia Mancini, Vincenzo Visco & Maria Rosaria Torrisi

Authors
  1. Cristina Vanni
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  2. Alessia Parodi
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  3. Patrizia Mancini
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  6. Maria Rosaria Torrisi
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  7. Alessandra Eva
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Correspondence to Alessandra Eva.

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Supplementary Information accompanies the paper on Oncogene's website (http://www.nature.com/onc).

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Vanni, C., Parodi, A., Mancini, P. et al. Phosphorylation-independent membrane relocalization of ezrin following association with Dbl in vivo. Oncogene 23, 4098–4106 (2004). https://doi.org/10.1038/sj.onc.1207509

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