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Human Molecular Genetics Advance Access published online on June 12, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm122
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton

Taru Muranen1,*, Mikaela Grönholm1, Aurelie Lampin2, Dominique Lallemand2, Fang Zhao1, Marco Giovannini2 and Olli Carpén1,3

1 Biomedicum Helsinki, Program of Neuroscience, Department of Pathology, 00014 University of Helsinki, Finland 2 Inserm U674, Fondation Jean Dausset-CEPH et Institut Universitaire d'Hématologie, 75010 Paris, France 3 Department of Pathology, University of Turku and Turku University Central Hospital, 20520 Turku, Finland

* Corresponding author: Taru Muranen, Biomedicum Helsinki C511, PL 63, 00014 University of Helsinki, Finland. Tel: +358919125651, Fax: +358947171964, E-mail: Taru.Muranen{at}helsinki.fi

Received March 9, 2007; Revised April 30, 2007; Accepted April 30, 2007

The lack of Neurofibromatosis 2 tumor suppressor protein merlin leads to the formation of nervous system tumors, specifically schwannomas and meningiomas. Merlin is considered to act as a tumor suppressor at the cell membrane, where it links transmembrane receptors to the actin cytoskeleton. Several tumor suppressors interact with another component of the cytoskeleton, the microtubules, in a regulated manner and control their dynamics. In this work, we identify merlin as a novel microtubule-organizing protein. We identify two tubulin-binding sites in merlin, one residing at the N-terminal FERM-domain and another at the C-terminal domain. Merlin's intramolecular association and phosphorylation of serine 518 regulate the interaction between merlin and tubulin. Analysis of cultured glioma cells indicates colocalization between merlin and microtubules especially during cell division. In primary mouse Schwann cells only minor colocalization at the cell periphery of interphase cells is seen. However, these cells drastically change their microtubule organization upon loss of merlin indicating a functional association of the proteins. Both in vitro assays and in vivo studies in Schwann cells indicate that merlin promotes tubulin polymerization. The results show that merlin plays a key role in the regulation of the Schwann cell microtubule cytoskeleton and suggest a mechanism by which loss of merlin leads to cytoskeletal defects observed in human schwannomas.


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