Bottom: Diagram of Merlin domains

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NF2 Tumor Suppressor Schwannomin/Merlin (Moesin-Ezrin-Radixin-like protein) 22q12

Bottom: Diagram of Merlin domains Top: The conserved FERM domain of ERM proteins links plasma membranes and actin filaments Bottom: Diagram of Merlin domains http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=94990 Shimizu T et al. J. Biol. Chem. 2002;277:10332-10336

Mutations mapped on the tertiary structure of merlin. Mutations mapped on the tertiary structure of merlin. A, nonsense mutations that result in truncated proteins are shown in red. B, missense mutations discussed in the text. Buried and exposed residues are colored red and blue, respectively. Residues in deletion mutations are colored green. Lys-79 involved in IP3 recognition is colored violet. A red arrow indicates the IP3-binding site found in radixin. Shimizu T et al. J. Biol. Chem. 2002;277:10332-10336 ©2002 by American Society for Biochemistry and Molecular Biology

In the absence of Merlin, EGFR with ligand is internalized and proliferative signals are transduced M. Curto and McClatchey, A. Merlin as a tumour suppressor. British Journal of Cancer (2008) 98(2), 256-262

Merlin regulates both proliferative signal receptors and the actin cytoskeleton M. Curto and McClatchey, A. Merlin as a tumour suppressor. British Journal of Cancer (2008) 98(2), 256-262

Effects of Merlin mutations depend on context (eg Effects of Merlin mutations depend on context (eg. the organism, types of cell contact) http://en.wikipedia.org/wiki/Drosophila http://www.telegraph.co.uk http://en.wikipedia.org/wiki/Zebrafish

NF2 leads to hearing and balance deterioration http://www.nfcalifornia.org/DiagnosticNF2.aspx

Tumors most commonly occur on the vestibular nerve and along the spinal cord 1 3 2 1. http://neurosurgery.ufl.edu 2. http://www.radpod.org 3. http://dx.doi.org/10.1016/j.neulet.2010.05.094

Treatment options include surgery and stereotactic radiotherapy, and maybe a monoclonal antibody? Mautner V-F et al. 2009 http://drarunlnaik.com/acoustic_tumor

References Curto M, McClatchey A. 2008. Merlin as a tumour suppressor. British Journal of Cancer 98(2): 256-262 McClatchey A, Giovannini M. 2005. Membrane organization and tumorigenesis – the NF2 tumor suppressor, Merlin. Genes Dev 19: 2265– 2277 Shimizu T et al. 2002. Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. J. Biol. Chem. 277: 10332-10336 Naik AL. “Acoustic Tumor (Vestibular schwannoma).” 2011. http://drarunlnaik.com/acoustic_tumor Mautner V-F et al. 2009. Bevacizumab induces regression of vestibular schwannomas in patients with neurofibromatosis type 2. Neuro Oncol. 12(1): 14-18 Zhou L, Hanemann CO. 2012. Merlin, a multi-suppressor from cell membrane to the nucleus. FEBS Lett. 586(10): 1402-1408