Abstract
Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by bilateral vestibular schwannomas and meningiomas. Merlin, the neurofibromatosis 2 tumor suppressor protein, is related to the ERM (ezrin, radixin, moesin) proteins and, like its family members, is thought to play a role in plasma membrane–cytoskeletal interactions. We report a novel protein as a merlin-specific binding partner that we have named magicin (merlin and Grb2 interacting cytoskeletal protein) and show that the two proteins interact in vitro and in vivo as well as colocalize beneath the plasma membrane. Magicin is a 24 kDa protein that is expressed in many cell lines and tissues. Magicin, similar to merlin, associates with the actin cytoskeleton as determined by cofractionation, immunofluorescence and electron microscopy. Analysis of the magicin sequence reveals binding motifs for the adaptor protein Grb2. Employing affinity binding, blot overlay and co-immunoprecipitation assays, we demonstrate an interaction between Grb2 and magicin. In addition, merlin is capable of forming a ternary complex with magicin and Grb2. These results support a role for merlin in receptor-mediated signaling at the cell surface, and may have implications in the regulation of cytoskeletal reorganization.
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Acknowledgements
We thank Drs J Settleman, N Ramesh and members of our laboratory for helpful comments on the manuscript. Our sincere thanks to Roberta Beauchamp for her help with the cytoskeletal preparations as well as helping with the figures. We also thank Johanna Lelke for her help with the mutant merlin constructs. This work was supported in part by National Institutes of Health Grant NS24279, Department of Defense Grant DAMD17-02-0647 and by funds from Neurofibromatosis Inc. (Massachusetts Chapter) and the Texas NF Foundation.
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Wiederhold, T., Lee, MF., James, M. et al. Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2. Oncogene 23, 8815–8825 (2004). https://doi.org/10.1038/sj.onc.1208110
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DOI: https://doi.org/10.1038/sj.onc.1208110
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